Methods for synthesizing organic sulfates from persulfate

Abstract

This invention discloses a method for preparing organic sulfates, comprising the following steps: using persulfate as the sulfate source, and achieving the functional group transformation of a free radical precursor compound through the free radical anion of the sulfate ion, thereby preparing the organic sulfate. This invention uses persulfate as the source and, through a free radical addition mechanism, acts on the free radical precursor substrate. Persulfate, as a sulfate free radical anion, participates in the functional group transformation of the organic compound, resulting in the efficient synthesis of organic sulfates.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of organic chemistry and the field of free radical chemistry, and discloses a novel radical sulfation reaction. BACKGROUND

[0002] Organic sulfate compounds are widely present in nature, including nucleosides, polypeptides, proteins, steroids, polysaccharides and pheromones, which play an important role in signal transduction, hormone regulation, molecular recognition and detoxification and other biological functions. At the same time, it is a very common drug modification method to perform post-sulfation treatment on natural drug molecules, such as heparin and chondroitin, which can obtain heparin sulfate and chondroitin sulfate after sulfation, thereby enhancing their intermolecular interaction and protein-receptor binding. It is worth noting that the emergence of the first antibiotic containing organic sulfate, sodium avibactam, has prompted the gradual reporting of other new beta-lactamase inhibitors. Since organic sulfate compounds play an important role in various important biological processes, their synthesis has become a focus of interest.

[0003] So far, the most common method for introducing sulfate groups into compounds is the nucleophilic addition reaction of hydroxyl or amine groups in the compound with the complex of sulfur trioxide (SO3)-organic amine. This method has good universality, but also has great limitations, that is, it completely depends on the nucleophilicity of the hydroxyl and amino functional groups in the substrate (Umesh R. Desai. Tetrahedron, 2010, 66, 2907-2918; Alan M. Jones. Chem. Commun., 2019, 55, 4319-4322), and sulfur trioxide is highly toxic and has poor biological compatibility. Other methods, such as esterification of hydroxyl-containing compounds with sulfuric acid and addition reaction of concentrated sulfuric acid with olefins, are theoretically feasible; the weak nucleophilicity of sulfate makes it have strict requirements for substrates and harsh reaction conditions, so these methods do not have much application value. Therefore, it is of great significance to develop a novel reaction mechanism, that is, a sulfation method that does not depend on the nucleophilicity of the substrate or the electrophilicity of the SO3 complex and has mild reaction conditions. SUMMARY

[0004] In order to solve the problems of limited substrates and high toxicity of sulfation reagents in traditional sulfation, the present application discloses an organic sulfate and a preparation method thereof.

[0005] The preparation method of the organic sulfate comprises the following steps: using a persulfate salt as a sulfate source, and realizing the conversion of functional groups of an organic compound through free radical anions of the sulfate, so as to prepare the organic sulfate.

[0006] Optionally, the persulfate salt has the following molecular general formula:

[0007]

[0008] wherein M is a counter cation.

[0009] An organic sulfate salt having the following general formula:

[0010]

[0011] wherein R includes substituted hydrocarbyl and substituted ar(hetero)yl groups, the substituents including >C1 hydrocarbyl, aryl, alkoxy, alkylthio, silyl, boryl, ester, amide, cyano, trifluoromethyl, aldehyde, nitro, alkenyl, alkynyl, azido, or halogen atoms, the number of substituents being one or more.

[0012] The present application uses persulfate as a source, through a free radical addition mechanism, acts on the free radical precursor substrate, and the persulfate as a sulfate radical anion participates in the functional group conversion of the organic, efficiently synthesizes organic sulfate salt. The persulfate used in the present application is K2S2O8, Na2S2O8, Ag2S2O8, (NH4)2S2O8, (Et4N)2S2O8, (Bu4N)2S2O8, (PyH)2S2O8, etc., and the applicable free radical precursor compounds include but are not limited to carboxylic acid, benzyl compound, olefin, halogen, alkyl boron, alkyl alcohol, 1,3-dicarbonyl compound, ar(hetero) ring, cyclopropane, etc. DETAILED DESCRIPTION

[0013] The technical solutions of the present application are specifically described below through a specific embodiment. The components or devices in the following embodiment are general standard components or components known to those skilled in the art, and their structure and principle can be known by those skilled in the art through technical manuals or through conventional experimental methods.

[0014] GENERAL DESCRIPTION

[0015] Abbreviations are used in the examples, which have the following meanings: Me is methyl, Ph is phenyl, Bu is butyl, B2Pin2 is pinacol diborane, TMS is trimethylsilyl, THF is tetrahydrofuran, DCM is dichloromethane, Acetone is acetone, DMF is N,N-dimethylformamide, and NMR is nuclear magnetic resonance.

[0016] The anhydrous and anaerobic experimental conditions involved in the present application are performed according to the Schlenk technical standards. The solvents used are purified and dried by standard methods before use, and the compounds used are commercially available or synthesized according to the existing literature methods and purified before use. In particular, the preparation method of alkyl boron compounds is described in the reference (Lei Liu. Angew. Chem. Int. Ed., 2012, 51, 528-53).

[0017] The present application is carried out by a brand-new free radical mechanism. The mechanism of all previous sulfation reactions is dependent on the nucleophilicity of the reaction initiator, and the addition reaction is carried out on the active sulfur trioxide complex (electrophilicity); or by means of the weak nucleophilicity of sulfate anion. The core of the present application is that the persulfate generates sulfate radical anion, so that it is not only an oxidant, but also an important sulfate functional group reagent. The mechanism of the sulfation reaction is as follows:

[0018]

[0019] Example one

[0020] This example focuses on a preparation method of organic sulfate compounds using carboxylic acid compounds as substrates and ammonium persulfate as a source of sulfate radical. The general formula is as follows:

[0021]

[0022] Wherein R includes substituted hydrocarbyl and substituted aryl(hetero) group. The substituents include ≥C1 hydrocarbyl, aryl, alkoxy, alkylthio, silicon, boron, ester, amide, cyano, trifluoromethyl, aldehyde, nitro, alkenyl, alkynyl, azido or halogen atom, and the number of substituents is one or more.

[0023] Ag(I) is any monovalent silver salt, including AgOAc, AgNO3, AgNO2, Ag2SO4, AgF, AgBr, AgI, AgOTf, AgBF4, AgPF6, AgClO4, Ag2CO3, AgTFA, etc. Ligand is a ligand, including monodentate, bidentate, tridentate and polydentate ligand. Base is an organic base or inorganic base, including LiHCO3, Li2CO3, Li3PO4, LiH2PO4, Li2HPO4, LiHC2O4, Li2C2O4, CH3COOLi, HCOOLi, LiOH, MeOLi, t-BuOLi, NaHCO3, Na2CO3, Na3PO4, NaH2PO4, Na2HPO4, NaHC2O4, Na2C2O4, CH3COONa, HCOONa, NaOH, MeONa, t-BuONa, KHCO3, K2CO3, K3PO4, KH2PO4, K2HPO4, KHC2O4, K2C2O4, CH3COOK, HCOOK, KOH, KO Li, t-BuOK, NH4HCO3, (NH4)2CO3, (NH4)3PO4, (NH4)H2PO4, (NH4)2HPO4, NH4HC2O4, (NH4)2C2O4, aqueous ammonia, triethylamine, diisopropylamine, trimethylamine, piperidine, pyridine. RT is room temperature, Na + resin is a sodium ion resin.

[0024] Example Two

[0025] This example focuses on a method for preparing an organic sulfate compound using a benzyl carbon-hydrogen compound as a substrate and ammonium persulfate as a sulfate source, which has the general formula as follows:

[0026]

[0027] wherein R 1 includes a hydrocarbon group of ≥C1, an aryl group, an alkoxy group, an alkylthio group, a silicon group, a boron group, an ester group, an amide group, a cyano group, a trifluoromethyl group, an aldehyde group, a nitro group, an alkenyl group, an alkynyl group, or a halogen atom, the number of substituents R 1 is 1-5; R 2 includes a hydrocarbon group of ≥C1, an aryl group, an alkoxy group, an alkylthio group, a silicon group, a boron group, an ester group, an amide group, a cyano group, a trifluoromethyl group, an aldehyde group, a nitro group, an alkenyl group, an alkynyl group. 3 includes a hydrocarbon group of ≥C1, an aryl group, an alkoxy group, an alkylthio group, a silicon group, a boron group, an ester group, an amide group, a cyano group, a trifluoromethyl group, an aldehyde group, a nitro group, an alkenyl group, an alkynyl group.

[0028] Ag(I), Ligand, Base, RT, Na + resin is the same as in Example One.

[0029] Example Three

[0030] This example focuses on a method for synthesizing organic bisulfate compounds using olefin compounds as substrates and potassium persulfate as a sulfate source. The general formula is as follows:

[0031]

[0032] wherein R 1 includes a ≥C1 hydrocarbon group, an aryl group, an alkoxy group, an alkylthio group, a silicon group, a boron group, an ester group, an amide group, a cyano group, a trifluoromethyl group, an aldehyde group, a nitro group, an alkenyl group, an alkynyl group, or a halogen atom, the number of substituents R 1 is 1-5; R 2 includes a ≥C1 hydrocarbon group, an aryl group, an alkoxy group, an alkylthio group, a silicon group, a boron group, an ester group, an amide group, a cyano group, a trifluoromethyl group, an aldehyde group, a nitro group, an alkenyl group, an alkynyl group; R 3 includes a ≥C1 hydrocarbon group, an aryl group, an alkoxy group, an alkylthio group, a silicon group, a boron group, an ester group, an amide group, a cyano group, a trifluoromethyl group, an aldehyde group, a nitro group, an alkenyl group, an alkynyl group.

[0033] Ag(I), Ligand, Base, RT, Na + resin as in Example One.

[0034] Example Four

[0035] This example focuses on a method for synthesizing organic sulfate compounds using olefin compounds as substrates and potassium persulfate as a sulfate source. The general formula is as follows:

[0036]

[0037] wherein R 1 includes a ≥C1 hydrocarbon group, an aryl group, an alkoxy group, an alkylthio group, a silicon group, a boron group, an ester group, an amide group, a cyano group, a trifluoromethyl group, an aldehyde group, a nitro group, an alkenyl group, an alkynyl group, or a halogen atom, the number of substituents R 1 is 1-5; R 2 includes a ≥C1 hydrocarbon group, an aryl group, an alkoxy group, an alkylthio group, a silicon group, a boron group, an ester group, an amide group, a cyano group, a trifluoromethyl group, an aldehyde group, a nitro group, an alkenyl group, an alkynyl group; R 3 includes a ≥C1 hydrocarbon group, an aryl group, an alkoxy group, an alkylthio group, a silicon group, a boron group, an ester group, an amide group, a cyano group, a trifluoromethyl group, an aldehyde group, a nitro group, an alkenyl group, an alkynyl group. - includes a cyano group (CN), a hydroxyl group (OH), a chlorine group (Cl), an azide group (N3).

[0038] Cu(I) is any monovalent copper salt, including CuI, CuCl, CuBr, Cu₂O, CuSCN, Cu(MeCN)₄BF₄, Cu(MeCN)₄OTf, and Cu(MeCN)₄PF₆; Cu(II) is any divalent copper salt, including CuI₂, CuCl₂, CuBr₂, CuO, Cu(OAc)₂, Cu(TFA), CuSO₄, Cu(OTf)₂, Cu(BF₄)₂, Cu(PF₆)₂, CuCO₃, Cu(NO₃)₂, and Cu(NO₂)₂. Ligand refers to the ligand, including monodentate, bidentate, tridentate, and polydentate ligands. RT is room temperature, and Na₂... + The resin is a sodium ion exchange resin.

[0039] Example 5

[0040] This embodiment focuses on the preparation method of an organic sulfate compound using a haloalkanes as a substrate and tetrabutylammonium persulfate as the sulfate source, the general formula of which is as follows:

[0041]

[0042] Y represents a halogen atom, including chlorine, bromine, and iodine. [Cu] represents any monovalent or divalent copper salt, including CuOAc, CuNO3, CuNO2, Cu2SO4, CuF, CuBr, CuI, CuOTf, CuBF4, CuPF6, CuClO4, Cu2CO3, CuTFA, Cu(OAc)2, Cu(NO3)2, Cu(NO2)2, CuSO4, CuF2, CuBr2, CuI2, Cu(OTf)2, Cu(BF4)2, Cu(PF6)2, CuCO3, Cu(TFA)2, etc. Ligand represents the ligand, including monodentate, bidentate, tridentate, and polydentate ligands. Bases can be organic or inorganic bases, including LiHCO3, Li2CO3, Li3PO4, LiH2PO4, Li2HPO4, LiHC2O4, Li2C2O4, CH3COOLi, HCOOLi, LiOH, MeOLi, t-BuOLi, NaHCO3, Na2CO3, Na3PO4, NaH2PO4, Na2HPO4, NaHC2O4, Na2C2O4, CH3COONa, HCOONa, NaOH, and Me. ONa, t-BuONa, KHCO3, K2CO3, K3PO4, KH2PO4, K2HPO4, KHC2O4, K2C2O4, CH3COOK, HCOOK, KOH, KOLi, t-BuOK, NH4HCO3, (NH4)2CO3, (NH4)3PO4, (NH4)H2PO4, (NH4)2HPO4, NH4HC2O4, (NH4)2C2O4, ammonia, triethylamine, diisopropylamine, trimethylamine, piperidine, pyridine. RT is room temperature, Na + The resin is a sodium ion exchange resin.

[0043] Example 6

[0044] This embodiment focuses on the preparation method of organic sulfate compounds using alkylboron compounds as substrates and ammonium persulfate as the sulfate source, with the following general formula:

[0045]

[0046] R is a substituted hydrocarbon group. Substituents include ≥C1 hydrocarbon groups, aryl, alkoxy, alkylthio, silyl, boron, ester, amide, cyano, trifluoromethyl, aldehyde, nitro, alkenyl, alkynyl, or halogen atoms, and there may be one or more substituents. [B] is boric acid (B(OH)2), trifluoroborate ( - BF3) and bis(pin) borate (Bpin), RT is at room temperature, Na + The resin is a sodium ion exchange resin.

[0047] Example 7

[0048] This embodiment focuses on the preparation method of organic sulfate compounds using hydroxyl compounds as substrates and potassium persulfate as the sulfate source, the general formula of which is as follows:

[0049]

[0050] R is the same as in Example 6, Na + The resin is a sodium ion exchange resin.

[0051] Example 8

[0052] This embodiment focuses on a method for preparing an organic sulfate compound using 1,3-dicarbonyl compounds as substrates and potassium persulfate as the sulfate source, the general formula of which is as follows:

[0053]

[0054] Where R 1 It includes ≥C1 aryl, alkyl, alkoxy, alkylthio, silyl, boronyl, ester, amide, cyano, trifluoromethyl, aldehyde, nitro, alkenyl, alkynyl or halogen atoms, with the number of substituents R1 being 1 to 5; R2 includes ≥C1 alkyl, aryl, alkoxy, alkylthio, silyl, boronyl, ester, amide, cyano, trifluoromethyl, aldehyde, nitro, alkenyl or alkynyl; R3 includes ≥C1 alkyl, aryl, alkoxy, alkylthio, silyl, boronyl, ester, amide, cyano, trifluoromethyl, aldehyde, nitro, alkenyl or alkynyl.

[0055] Ag(I) represents any monovalent silver salt, including AgOAc, AgNO3, AgNO2, Ag2SO4, AgF, AgBr, AgI, AgOTf, AgBF4, AgPF6, AgClO4, Ag2CO3, AgTFA, etc. Ligand represents the ligand, including monodentate, bidentate, tridentate, and polydentate ligands.

[0056] Example 9

[0057] This embodiment focuses on the preparation method of an aryl sulfate compound using (hetero)aromatic hydrocarbons as substrates and ammonium persulfate as the sulfate source, the general formula of which is as follows:

[0058]

[0059] Where R 1 Including ≥C1 hydrocarbon, aryl, alkoxy, alkylthio, silyl, boron, ester, amide, cyano, trifluoromethyl, aldehyde, nitro, alkenyl, alkynyl, or halogen atoms, and substituents R. 1 The quantity is 1 to 5;

[0060] Ag(I) represents any monovalent silver salt, including AgOAc, AgNO3, AgNO2, Ag2SO4, AgF, AgBr, AgI, AgOTf, AgBF4, AgPF6, AgClO4, Ag2CO3, AgTFA, etc. Ligand represents the ligand, including monodentate, bidentate, tridentate, and polydentate ligands. Na + The resin is a sodium ion exchange resin.

[0061] Example 10

[0062] This embodiment focuses on a method for preparing an organic sulfate compound using arylcyclopropane compounds as substrates and ammonium persulfate as the sulfate source, the general formula of which is as follows:

[0063]

[0064] Where R 1 ,R 2 ,R 3 ,R 4 ,R 5 ,R 6 The structure includes H, aryl, ≥C1 hydrocarbon group, alkoxy, alkylthio, silyl, boron, ester, amide, cyano, trifluoromethyl, aldehyde, nitro, alkenyl, alkynyl or halogen atom, and substituent R. 1 The quantity ranges from 1 to 5.

[0065] Ag(I) represents any monovalent silver salt, including AgOAc, AgNO3, AgNO2, Ag2SO4, AgF, AgBr, AgI, AgOTf, AgBF4, AgPF6, AgClO4, Ag2CO3, AgTFA, etc. Ligand represents the ligand, including monodentate, bidentate, tridentate, and polydentate ligands. Na + The resin is a sodium ion exchange resin.

[0066] Experimental Example 1: Preparation of Sodium 4-Chlorobenzyl Sulfate

[0067]

[0068] Add 0.2 mmol of 4-chlorophenylacetic acid, 0.01 mmol of silver nitrite, 0.01 mmol of ligand, 0.6 mmol of ammonium persulfate, 0.24 mmol of tetrabutylammonium bisulfate, and 0.24 mmol of potassium dihydrogen phosphate sequentially to a 4 mL reaction flask. After the additions, seal the 4 mL reaction flask, evacuate it, and then purge it with argon gas. Repeat this process three times. Finally, add 1 mL of dichloromethane to the flask and allow it to react at room temperature for 11 hours. After the reaction is complete, quench the reaction with 200 mg of sodium bicarbonate, and then filter to collect the organic phase. Concentrate the organic phase and perform column chromatography. Separate tetrabutylammonium 4-chlorobenzyl sulfate using a dichloromethane to methanol eluent at a volume ratio of 20:1. Finally, perform ion exchange to obtain sodium 4-chlorobenzyl sulfate (35.7 mg, 73%). 1 H NMR (400MHz, CD3OD, 298K, δ): 7.40 (d, J = 8.8Hz, 2H), 7.34 (d, J = 8.8Hz, 2H), 4.99 (s, 2H); 13 C NMR (101MHz, CD3OD, 298K, δ): 136.6, 134.6, 130.4, 129.3, 69.6.

[0069] Experimental Example 2: Preparation of Sodium 4-Fluorobenzyl Sulfate

[0070]

[0071] The experimental procedure is shown in Example 1, 4-fluorobenzyl sulfate sodium (34.7 mg, 76%). 1 H NMR (400MHz, CD3OD, 298K, δ): 7.47-7.39 (m, 2H), 7.13-7.02 (m, 2H), 4.99 (s, 2H); 13 C NMR (101MHz, CD3OD, 298K, δ): 164.0 (d, J = 244.8Hz), 134.0, 131.2 (d, J = 8.3Hz), 116.0 (d, J = 21.8Hz), 70.0; 19 F NMR (376MHz, CD3OD, 298K, δ): -116.67.

[0072] Experimental Example 3: Preparation of Sodium 4-Bromobenzyl Sulfate

[0073]

[0074] The experimental procedure is shown in Example 1, using sodium 4-bromobenzyl sulfate (40.1 mg, 72%). 1H NMR (400MHz, CD3OD, 298K, δ): 7.50 (d, J = 8.4Hz, 2H), 7.34 (d, J = 8.4Hz, 2H), 4.97 (s, 2H); 13 C NMR (101MHz, CD3OD, 298K, δ): 137.3, 132.5, 130.8, 122.8, 69.8. Example 4: Preparation of Sodium 4-Nitrobenzyl Sulfate

[0075]

[0076] The experimental procedure is shown in Example 1, 4-nitrobenzyl sulfate (31.6 mg, 62%). 1 H NMR (400MHz, CD3OD, 298K, δ): 7.50 (d, J = 8.4Hz, 2H), 7.34 (d, J = 8.4Hz, 2H), 4.97 (s, 2H); 13 C NMR (101 MHz, CD3OD, 298 K, δ): 137.3, 132.5, 130.8, 122.8, 69.8. Example 5: Preparation of sodium 4-methanesulfonyl benzyl sulfate.

[0077]

[0078] The experimental procedure is shown in Example 1, 4-methanesulfonyl benzyl sulfate sodium (36.9 mg, 64%). 1 H NMR (400MHz, CD3OD, 298K, δ): 7.95 (d, J = 8.4Hz, 2H), 7.68 (d, J = 8.4Hz, 2H), 5.13 (s, 2H), 3.12 (s, 3H); 13 C NMR (101MHz, CD3OD, 298K, δ): 144.7, 141.3, 129.3, 128.5, 69.4, 44.4.

[0079] Experimental Example 6: Preparation of Sodium 1,4-benzodioxane-2-sulfate

[0080]

[0081] The experimental procedure is shown in Example 1, using sodium 1,4-benzodioxane-2-sulfate (40.2 mg, 75%). 1 H NMR (400MHz, CD3OD, 298K, δ): 6.93-6.81 (m, 4H), 6.04 (s, 1H), 4.20 (ddd, J = 73.8, 14.2, 2Hz, 2H); 13C NMR (101MHz, CD3OD, 298K, δ): 144.6, 142.1, 123.1, 122.8, 118.7, 117.8, 92.8, 66.9.

[0082] Experimental Example 7: Preparation of Sodium 4-Methoxybenzyl Sulfate

[0083]

[0084] The experimental procedure is shown in Example 1, using sodium 4-methoxybenzyl sulfate (20.2 mg, 42%). 1 H NMR (400MHz, CD3OD, 298K, δ): 7.33 (d, J = 8.8Hz, 2H), 6.89 (d, J = 8.8Hz, 2H), 4.94 (s, 2H), 3.79 (s, 3H); 13 C NMR (101 MHz, CD3OD, 298 K, δ): 161.1, 130.9, 129.8, 114.7, 70.7, 55.7. Example 8: Preparation of Sodium 4-Iodobenzylsulfate

[0085]

[0086] The experimental procedure is shown in Example 1, 4-iodobenzyl sulfate sodium (37.0 mg, 55%). 1 H NMR (400MHz, CD3OD, 298K, δ): 7.70 (d, J = 8Hz, 2H), 7.20 (d, J = 8.4Hz, 2H), 4.96 (s, 2H); 13 C NMR (101 MHz, CD3OD, 298 K, δ): 138.6, 137.9, 130.9, 94.0, 69.9. Example 9: Preparation of sodium α-isopropyl-4-chlorobenzyl sulfate.

[0087]

[0088] The experimental procedure is shown in Example 1, using sodium α-isopropyl-4-chlorobenzyl sulfate (35.0 mg, 65%). 1 H NMR (400MHz, CD3OD, 298K, δ): 7.34-7.27 (m, 4H), 5.00 (d, J = 6.5Hz, 1H), 2.04 (dq, J = 13.5, 6.7Hz, 1H), 0.96 (d, J = 6.8Hz, 3H), 0.84 (d, J = 6.8Hz, 3H); 13 C NMR (101MHz, CD3OD, 298K, δ): 140.9, 133.9, 129.8, 128.8, 85.8, 35.8, 18.9, 18.5.

[0089] Experiment 10: Preparation of Sodium 4-Cyanobenzyl Sulfate

[0090]

[0091] The experimental procedure is shown in Example 1, 4-cyanobenzyl sulfate sodium (24.5 mg, 52%). 1 H NMR (400MHz, CD3OD, 298K, δ): 7.72 (d, J = 8.4Hz, 2H), 7.60 (d, J = 8.8Hz, 2H), 5.09 (s, 2H); 13 C NMR (101MHz, CD3OD, 298K, δ): 144.0, 133.3, 129.3, 119.7, 112.5, 69.4.

[0092] Experimental Example 11: Preparation of Sodium α-phthalimide benzyl sulfate

[0093]

[0094] The experimental procedure is shown in Example 1, using sodium α-phthalimide benzyl sulfate (47.6 mg, 67%). 1 H NMR (400MHz, CD3OD, 298K, δ): 7.90-7.78 (m, 4H), 7.54 (d, J = 7.6Hz, 2H), 7.40-7.30 (m, 3H), 7.29 (s, 1H); 13 C NMR (101MHz, CD3OD, 298K, δ): 168.3, 137.8, 135.7, 133.1, 129.4, 129.2, 127.1, 124.5, 78.7.

[0095] Experimental Example: Preparation of Sodium Dodeca-α-Allyl-4-Fluorobenzyl Sulfate

[0096]

[0097] The experimental procedure is shown in Example 1, α-allyl-4-fluorobenzyl sulfate sodium (25.8 mg, 48%). 1 H NMR (400MHz, CD3OD, 298K, δ): 7.38 (dd, J=8.7, 5.5Hz, 2H), 7.03 (t, J=8.8Hz, 2H), 5.72 (ddt, J=17. 2,10.2,7.0Hz,1H),5.31(t,J=6.6Hz,1H),5.04-4.95(m,2H),2.68(dtd,J=28.4,14.2,6.8Hz,2H); 13C NMR (101MHz, CD3OD, 298K, δ): 163.6 (d, J = 243.9Hz), 138.3, 134.7, 129.7 (d, J = 8.1Hz), 118.1, 115.6 (d, J = 21.6Hz), 80.5), 42.7; 19 F NMR (376MHz, CD3OD, 298K, δ): -117.54 (tt, J=8.9, 5.4Hz).

[0098] Experimental Example XIII: Preparation of Sodium 6-chloropyridine-3-methylsulfate

[0099]

[0100] The experimental procedure is shown in Example 1, using sodium 6-chloropyridine-3-methylsulfate (24.6 mg, 50%). 1 H NMR (400MHz, CD3OD, 298K, δ): 8.41 (d, J = 2.0Hz, 1H), 7.89 (dd, J = 8, 2.4Hz, 1H), 7.45 (d, J = 8Hz, 1H), 5.05 (s, 2H); 13 C NMR (101MHz, CD3OD, 298K, δ): 151.7, 150.0, 140.6, 133.7, 125.4, 67.1.

[0101] Experimental Example 14: Preparation of Sulfated Zaltopiprofen

[0102]

[0103] The experimental procedure is shown in Example 1, using zatopobuprofen sodium sulfate (41.0 mg, 55%). 1 H NMR (400MHz, CD3OD, 298K, δ): 8.13 (dd, J=8.0, 1.2Hz, 1H), 7.66-7.61 (m, 2H), 7.50 (ddd, J=15.2 ,9.2,1.6Hz,2H),7.39-7.29(m,2H),5.46(q,J=6.8Hz,1H),4.36(s,2H),1.58(d,J=6.4Hz,3H); 13 C NMR (101MHz, CD3OD, 298K, δ): 193.1, 146.8, 141.7, 138.9, 137.2, 134.6, 133.9, 132.3, 132.1, 131.9, 128.0, 126.2, 77.1, 51.7, 23.7.

[0104] Experimental Example 15: Preparation of Sulfated Loxoprofen

[0105]

[0106] The experimental procedure is shown in Example 1, for sulfated loxoprofen (34.6 mg, 54%). 1 H NMR (400MHz, CD3OD, 298K, δ): 7.32 (d, J = 8.0Hz, 2H), 7.14 (d, J = 8.4Hz, 2H), 5.44 (q, J = 6.8Hz, 1H), 3.05 (dd, J = 14.0, 4.4Hz, 1H), 2.53(dd,J=13.7,9.3Hz,1H),2.45-2.25(m,2H),2.05(dddd,J=10.2,8.1,7.1,5.3Hz,2H),1.98-1.70(m,2H),1.63-1.52(m,4H); 13 C NMR (101MHz, CD3OD, 298K, δ): 222.8, 141.9, 140.5, 129.8, 127.2, 77.8, 52.0, 39.0, 36.1, 30.0, 23.5, 21.4.

[0107] Experimental Example 16: Preparation of Sodium α-Methyl-4-phenylbenzylsulfate

[0108]

[0109] Add 0.2 mmol of 4-ethylbiphenyl, 0.02 mmol of silver nitrite, 0.02 mmol of ligand, 0.6 mmol of ammonium persulfate, and 0.3 mmol of triethylamine sequentially to a 4 mL reaction flask. After the additions are complete, seal the 4 mL reaction flask, evacuate it, and then purge it with argon gas. Repeat this process three times. Finally, add 1 mL of dichloromethane to the flask and allow it to react at room temperature for 8 hours. After the reaction is complete, quench the reaction with 200 mg of sodium bicarbonate, and then filter to collect the organic phase. Concentrate the organic phase and perform column chromatography. Separate α-methyl-4-phenylbenzyl sulfate tetrabutylammonium using a dichloromethane to methanol eluent in a volume ratio of 20:1. Finally, perform ion exchange to obtain sodium α-methyl-4-phenylbenzyl sulfate (48.0 mg, 80%). 1 HNMR (400MHz, CD3OD, 298K, δ): 7.58 (td, J=6.9, 6.4, 1.9Hz, 4H), 7.49 (d, J=8.1Hz, 2H), 7. 41(dd,J=8.3,6.9Hz,2H),7.34–7.27(m,1H),5.52(q,J=6.6Hz,1H),1.64(d,J=6.5Hz,3H); 13C NMR (101MHz, MHz, CD3OD, 298K, δ): 143.1, 142.1, 141.6, 129.8, 128.2, 127.9, 127.8, 127.6, 77.7, 23.6.

[0110] Experimental Example 17: Preparation of Sodium α-methyl-4-phthalimide benzyl sulfate

[0111]

[0112] The experimental procedure is shown in Example 16. Sodium α-methyl-4-phthalimide benzyl sulfate (80%) 1 H-NMR yield). 1 H NMR (400MHz, DMSO-d6, 298K, δ): 7.99–7.88 (m, 4H), 7.48 (d, J = 8.3Hz, 2H), 7.38 (d, J = 8.3Hz, 2H), 5.30 (q, J = 6.6Hz, 1H), 1.48 (d, J = 6.6Hz, 3H); 13 C NMR (101MHz, DMSO-d6, 298K, δ): 167.1, 144.0, 134.8, 131.6, 130.4, 126.9, 126.3, 123.4, 73.2, 23.5.

[0113] Experimental Example 18: Preparation of Tetrabutylammonium α-propyl-4-(4-cyanophenyl)benzylsulfonate

[0114]

[0115] The experimental procedure is shown in Example 16. α-propyl-4-(4-cyanophenyl)benzylsulfonate tetrabutylammonium (65%) 1 H-NMR yield). 1 H NMR (400MHz, CDCl3, 298K, δ): 7.67–7.60 (m, 4H), 7.50–7.44 (m, 4H), 5.33 (t, J=6.7Hz, 1H), 3.24–3.11 (m, 8H), 1.95 (dddd, J=13.6, 10.5 ,6.9,5.3Hz,1H),1.74(ddt,J=13.4,10.2,6.0Hz,1H),1.62–1.47(m,8H),1.35(h,10H),0.92(t,J=7.3Hz,12H),0.85(t,J=7.4Hz,3H); 13C NMR (101MHz, CDCl3, 298K, δ): 145.6, 143.8, 137.1, 132.4, 127.4, 127.3, 126.51, 118.9, 110.2, 78.4, 58.4, 39.7, 23.7, 19.5, 18.4, 13.9, 13.5.

[0116] Experimental Example 19: Preparation of Sodium α-Methyl-4-difluoromethoxybenzyl sulfate

[0117]

[0118] The experimental procedure is described in Example 16. Sodium α-methyl-4-difluoromethoxybenzyl sulfate (60%) 1 H-NMR yield). 1 HNMR (400MHz, CD3OD, 298K, δ): 7.44 (d, J = 8.6Hz, 2H), 7.10 (d, J = 8.7Hz, 2H), 6.79 (t, J = 74.3Hz, 1H), 5.46 (q, J = 6.6Hz, 1H), 1.59 (d, J = 6.6Hz, 3H); 13 C NMR (101MHz, CD3OD, 298K, δ): 152.1, 141.1, 128.7, 119.8, 117.7 (t, J = 257.4Hz), 77.2, 23.6; 19 F NMR (376MHz, CD3OD, 298K, δ): -83.13.

[0119] Experimental Example 20: Preparation of sodium α-methyl-4-((4-ethylbenzoyl)oxy)benzyl sulfate

[0120]

[0121] The experimental procedure is described in Example Sixteen. Sodium α-methyl-4-((4-ethylbenzoyl)oxy)benzyl sulfate (45%) 1 H-NMR yield). 1 H NMR (400MHz, CD3OD, 298K, δ): 8.08 (d, J = 8.0Hz, 2H), 7.50 (d, J = 8.4Hz, 2H), 7.38 (d, J = 8.1Hz, 2H), 7.18 (d ,J=8.4Hz,2H),5.51(q,J=6.6Hz,1H),2.75(q,J=7.6Hz,2H),1.63(d,J=6.6Hz,3H),1.27(t,J=7.6Hz,3H); 13C NMR (101MHz, CD3OD, 298K, δ): 166.7, 152.2, 151.7, 141.8, 131.2, 129.3, 128.3, 128.1, 122.5, 77.4, 29.9, 23.7, 15.7.

[0122] Experimental Example 21: Preparation of Tetrabutylammonium α-Methyl-4-(1-nitro-4-methylbenzyl)sulfonylammonium sulfate

[0123]

[0124] The experimental procedure is shown in Example 16. α-Methyl-4-(1-nitro-4-methylbenzyl)benzylsulfonate tetrabutylammonium (72%) 1 H-NMR yield). 1 H NMR (400MHz, CDCl3, 298K, δ): 7.59 (s, 1H), 7.47 (d, J = 7.9Hz, 2H), 7.38 (d, J = 1.7Hz, 1H), 7.28 (d, J = 7.8Hz, 1H), 7.19 (d, J = 7.9Hz, 2H), 5.54 (d,J=6.5Hz,1H),3.30–2.93(m,8H),2.43(s,3H),1.64(d,J=6.6Hz,3H),1.61–1.48(m,8H),1.35(h,J=7.4Hz,8H),0.94(t,J=7.3Hz,12H); 13 C NMR (101MHz, CDCl3): 149.0, 143.8, 138.44, 135.8, 133.3, 133.0, 131.8, 127.5, 126.6, 124.1, 74.7, 58.6, 23.8, 23.1, 20.8, 19.6, 13.5.

[0125] Experimental Example 22: Preparation of Tetrabutylammonium α-cyano-4-methoxybenzyl sulfate

[0126]

[0127] The experimental procedure is shown in Example 16. α-Methyl-4-(1-nitro-4-methylbenzyl)benzylsulfonate tetrabutylammonium (89%) 1 H-NMR yield). 1H NMR (400MHz, CDCl3, 298K, δ): 7.41 (d, J = 8.7Hz, 2H), 6.81 (d, J = 8.8Hz, 2H), 5.92 (s, 1H), 3.73 (s,3H),3.14–3.07(m,8H),1.56–1.45(m,8H),1.30(h,J=7.4Hz,8H),0.88(t,J=7.3Hz,12H); 13 C NMR (101MHz, CDCl3, 298K, δ): 160.1, 128.7, 125.9, 118.2, 113.7, 65.6, 58.1, 55.1, 23.5, 19.3, 13.4.

[0128] Experimental Example 23: Preparation of Tetrabutylammonium α-methylformic acid-2-methoxybenzyl sulfate

[0129]

[0130] The experimental procedure is shown in Example 16, α-methylformic acid-2-methoxybenzyl sulfate tetrabutylammonium (85%). 1 H-NMR yield). 1 H NMR (400MHz, CDCl3, 298K, δ): 7.50 (dd, J=7.7, 1.7Hz, 1H), 7.20 (ddd, J=8.3, 7.4, 1.7Hz, 1H), 6.85 (td, J=7.5, 1.1Hz, 1H), 6.79 (dd, J=8.3 ,1.0Hz,1H),6.08(s,1H),3.74(s,3H),3.61(s,3H),3.20–3.11(m,8H),1.57–1.45(m,8H),1.32(h,J=7.4Hz,8H),0.90(t,J=7.3Hz,12H); 13 C NMR (101MHz, CDCl3, 298K, δ): 171.5, 156.7, 129.4, 129.5, 125.5, 120.4, 110.9, 71.6, 58.2, 55.8, 52.0, 23.8, 19.5, 13.67.

[0131] Experimental Example 24: Preparation of Tetrabutylammonium α-diethoxyphosphate-4-methoxybenzyl sulfate

[0132]

[0133] The experimental procedure is shown in Example 16. α-Diethoxyphosphate-4-methoxybenzylsulfonate tetrabutylammonium (52%) 1 H-NMR yield). 1H NMR (400MHz, CDCl3, 298K, δ): 7.44 (dd, J=8.8, 2.1Hz, 2H), 6.79 (d, J=8.5Hz, 2H), 5.67 (d, J=14.8Hz, 1H), 4.20–4.07 (m, 4H ),3.74(s,3H),3.18–3.06(m,8H),1.53(p,J=8.1,7.6Hz,8H),1.35(p,J=7.4Hz,8H),1.22(t,6H),0.94(t,J=7.3Hz,12H); 13 C NMR (101MHz, CDCl3, 298K, δ): 159.22, 129.3 (d, J = 6.0Hz), 113.4 (d, J = 2.2Hz), 74.0(d,J=168.0Hz),63.8,56.9(d,J=327.0Hz),23.9,19.7,16.5,16.4,13.7; 31 P NMR (162MHz, CDCl3, 298K, δ): 18.34.

[0134] Experimental Example 25: Preparation of Sodium 5-methoxy-3-oxo-2,3-dihydro-1H-indene-1-ylsulfate

[0135]

[0136] The experimental procedure is described in Example Sixteen. Sodium 5-methoxy-3-oxo-2,3-dihydro-1H-indene-1-yl sulfate (90%) 1 H-NMR yield). 1 H NMR (400MHz, DMSO-d6, 298K, δ): 7.70 (d, J=8.3Hz, 1H), 7.32 (dd, J=8.5, 2.7Hz, 1H), 7.08 (s, 1H), 5. 69(dd,J=6.5,2.4Hz,1H),3.82(s,3H),3.05(dd,J=19.1,6.7Hz,1H),2.69(dd,J=19.0,2.5Hz,1H); 13 C NMR (101MHz, DMSO-d6, 298K, δ): 202.8, 160.5, 146.1, 137.9, 128.3, 123.5, 104.1, 71.1, 55.7, 45.3.

[0137] Experiment 20: Preparation of Indomethacin Sulfated

[0138]

[0139] The experimental procedure is shown in Example 16, using tetrabutylammonium indomethacin sulfate (40%). 1 H-NMR yield). 1 H NMR (400MHz, CDCl3, 298K, δ): 7.64 (d, J = 8.5Hz, 2H), 7.39 (d, J = 8.5Hz, 2H), 6.92 (d, J = 2.5Hz, 1H), 6.74 (d, J = 9.0Hz, 1H), 6.64 (dd, J = 9.0, 2.5Hz ,1H),5.19(s,2H),3.91(s,2H),3.78(s,3H),3.64(s,3H),3.15–3.06(m ,8H),1.56–1.43(m,8H),1.27(h,J=7.3Hz,8H),0.88(t,J=7.3Hz,12H); 13 C NMR (400MHz, CDCl3, 298K, δ):171.6,168.2,155.8,139.2,135.3,133.8,131.4,131.3,1 30.1,129.0,116.0,114.8,113.0,101.7,59.2,58.3,55.7,52.1,30.0,23.8,19.6,13.6.

[0140] Experiment 27: Preparation of Tetrabutylammonium α-phenyl-4-chlorobenzyl sulfate

[0141]

[0142] The experimental procedure is shown in Example 16, α-phenyl-4-chlorobenzyl sulfate tetrabutylammonium (68%). 1 H-NMR yield). 1 H NMR (400MHz, CDCl3, 298K, δ):7.34–7.29(m,4H),7.24–7.15(m,5H),6.35(s,1H),3 .07–2.96(m,8H),1.50–1.37(m,8H),1.26(h,J=7.4Hz,8H),0.89(t,J=7.3Hz,12H); 13 C NMR (101MHz, CDCl3, 298K, δ): 142.0, 141.2, 132.5, 129.0, 128.0, 127.9, 127.5, 127.2, 79.0, 58.2, 23.7, 19.6, 13.6.

[0143] Experimental Example 28: Preparation of Tetrabutylammonium 1-(2-acetoxyphenyl)carbonylbenzofuran butylsulfate

[0144]

[0145] The experimental procedure is described in Example 16. 1-(2-acetoxyphenyl)carbonylbenzofuran butylsulfonate tetrabutylammonium (54%) 1 H-NMR yield). 1 H NMR (400MHz, CDCl3, 298K, δ): 7.87 (d, J = 8.4Hz, 2H), 7.44 (d, J = 8.2Hz, 1H), 7.26–7.20 (m, 1H), 7.14–7.07 (m, 4H), 5.67 (t, J = 7.2Hz, 1H), 3.14–3.02(m,8H),2.28(s,3H),2.15–2.03(m,1H),2.00–1.89(m,1H),1.54–1.39(m,9H),1.27(h,J=7.4Hz,9H),0.87(t,J=7.2Hz,15H); 13 C NMR (101MHz, CDCl3, 298K, δ): 190.6, 168.8, 162.3, 154.1, 153.7, 136.5, 131.3, 126.5, 124. 7,123.3,121.6,121.4,118.0,111.5,70.4,58.2,36.3,23.8,21.2,19.6,18.6,13.9,13.6.

[0146] Experimental Example 29: Preparation of Sodium α-methyl-4-(5-(ethoxycarbonyl)thiophene)benzylsulfate

[0147]

[0148] The experimental procedure is described in Example Sixteen. Sodium α-methyl-4-(5-(ethoxycarbonyl)thiophene)benzyl sulfate (56%) 1 H-NMR yield). 1 H NMR (400MHz, CD3OD, 298K, δ): 7.75 (d, J = 3.9 Hz, 1H), 7.66 (d, J = 8.3 Hz, 2H), 7.48 (d, J = 8.3 Hz, 2H), 7.42 (d ,J=3.9Hz,1H),5.49(q,J=6.6Hz,1H),4.34(q,J=7.1Hz,2H),1.61(d,J=6.6Hz,3H),1.37(t,J=7.1Hz,3H); 13 C NMR (101MHz, CD3OD, 298K, δ): 163.7, 152.4, 145.1, 135.6, 133.7, 133.2, 127.9, 127.0, 125.0, 77.4, 62.4, 23.6, 14.6.

[0149] Experimental Example: Preparation of Epidermo-2-methylsulfated Epidermo-2-ethyl

[0150]

[0151] The experimental procedure is shown in Example 16. Sulfated epidermal ketone (93%) 1 H-NMR yield). 1 H NMR (400MHz, CDCl3, 298K, δ): 7.35 (d, J = 8.2Hz, 2H), 6.77 (d, J = 8.3Hz, 2H), 5.63 (s, 1H), 4.65 (tt, J = 10.8, 4.9H z,1H),3.73(s,3H),3.23–3.11(m,8H),2.38(dd,J=19.2,8.8Hz,1H),1.99(dd,J=19.0,9.2Hz,1H),1.93–1.83( m,1H),1.71(dt,J=26.1,10.7Hz,4H),1.51(tt,J=17.5,9.8Hz,13H),1.33(h,J=6.9Hz,10H),1.22(tt,J=14.3, 7.1Hz,5H),1.08(t,J=7.3Hz,1H),0.91(t,J=7.3Hz,14H),0.78(d,J=13.8Hz,6H),0.64(dt,J=11.1,5.4Hz,1H); 13 CNMR (101MHz, CDCl3, 298K, δ):170.43,170.41,159.4,129.0,128.7,128.7,113.5,76.2,73.9,58.3,55.2,54.3,51.4,47.8,44 .8,44.7,36.7,36.6,35.9,35.6,35.0,33.7,33.5,31.5,30.8,28.3,28.2,27.3,27.1,23.8,21.8,20.4,19.6,13.8,13.7,12.3.

[0152] Experimental Example 31: Preparation of Sodium 1-Phenylacetane-1,2-Disulfate

[0153]

[0154] Add styrene (0.2 mmol), silver carbonate (0.01 mmol), ligand (0.02 mmol), potassium persulfate (0.6 mmol), and tetrabutyl potassium persulfate (0.2 mmol) sequentially to a 4 mL reaction flask. After the additions, seal the 4 mL reaction flask, evacuate it, and then purge it with argon gas. Repeat this process three times. Finally, add 1 mL of dichloromethane to the flask and allow it to react at room temperature for 10 hours. After the reaction is complete, add 200 mg of sodium bicarbonate to quench the reaction, and then filter to collect the organic phase. Concentrate the organic phase and perform column chromatography. Separate 1-phenylethane-1,2-disulfate tetrabutylammonium using a dichloromethane to methanol eluent ratio of 20:1. Finally, perform ion exchange to obtain sodium 1-phenylethane-1,2-disulfate (80%). 1 H-NMR yield). 1 H NMR (400MHz, D2O, 298K, δ): 7.58–7.40 (m, 5H), 5.58 (dd, J = 6.7, 4.4Hz, 1H), 4.34 (dd, J = 11.1, 6.8Hz, 1H), 4.27 (dd, J = 11.1, 4.3Hz, 1H); 13 C NMR (101MHz, D2O, 298K, δ): 136.2, 128.9, 128.7, 126.8, 78.7, 70.0.

[0155] Experimental Example 32: Preparation of Sodium 1-(4-phenyl)phenylethane-1,2-disulfate

[0156]

[0157] The experimental procedure is described in Example 31, using sodium 1-(4-phenyl)phenylethane-1,2-disulfate (80%). 1 H-NMR yield). 1 H NMR(400MHz,D2O,298K,δ):7.69(d,J=7.6Hz,1H),7.58–7.46(m,5H),7.42(d,J=7 .2Hz,2H),7.31(d,J=6.8Hz,1H),5.66(dd,J=6.4,4.8Hz,1H),4.19–4.10(m,2H); 13 C NMR (101MHz, D2O, 298K, δ): 141.0, 139.8, 133.7, 129.9, 129.3, 128.6, 128.5, 128.0, 127.6, 127.0, 75.8, 69.6.

[0158] Experimental Example 33: Preparation of Sodium 1-(3-chlorophenyl)ethane-1,2-disulfate

[0159]

[0160] The experimental procedure is described in Example 31. Sodium 1-(3-chlorophenyl)ethane-1,2-disulfate (58%) 1 H-NMR yield). 1 HNMR(400MHz,D2O,298K,δ):7.56(s,1H),7.48–7.41(m,3H),5.59(dd,1H),4.38–4.26(m,2H); 13 C NMR (101MHz, D2O, 298K, δ): 138.3, 133.8, 130.2, 128.8, 126.8, 125.2, 77.9, 69.8.

[0161] Experimental Example 34: Preparation of Sodium 1-(3-bromophenyl)ethane-1,2-disulfate

[0162]

[0163] The experimental procedure is described in Example 31. Sodium 1-(3-chlorophenyl)ethane-1,2-disulfate (66%) 1 H-NMR yield). 1 HNMR (400MHz, D2O, 298K, δ): 7.64 (d, J = 8.4Hz, 2H), 7.41 (d, J = 8.4Hz, 2H), 5.56 (dd, J = 4.4, 2.0Hz, 1H), 4.29 (qd, J = 11.1, 5.5Hz, 2H); 13 C NMR (101MHz, D2O, 298K, δ): 135.5, 131.6, 128.7, 122.2, 78.0, 69.7.

[0164] Experimental Example 35: Preparation of Sodium 1-(4-(methoxycarbonyl)phenyl)ethane-1,2-disulfate

[0165]

[0166] The experimental procedure is described in Example 31. Sodium 1-(4-(methoxycarbonyl)phenyl)ethane-1,2-disulfate (74%) 1 H-NMR yield). 1 H NMR (400MHz, D2O, 298K, δ): 8.08 (d, J = 8.4Hz, 2H), 7.64 (d, J = 8.4Hz, 2H), 5.71-5.66 (m, 1H), 4.40-4.31 (m, 2H), 3.97 (s, 3H); 13C NMR (101MHz, D2O, 298K, δ): 169.0, 141.9, 129.7, 129.7, 78.0, 69.8, 52.7.

[0167] Experimental Example 36: Preparation of Sodium 1-(4-fluorophenyl)ethane-1,2-disulfate

[0168]

[0169] The experimental procedure is described in Example 31. Sodium 1-(4-fluorophenyl)ethane-1,2-disulfate (72%) 1 H-NMR yield). 1 HNMR(400MHz,D2O,298K,δ):7.54–7.48(m,1H),7.20(t,J=8.9Hz,1H),5.58(dd ,J=6.7,4.5Hz,1H),4.32(dd,J=11.1,6.7Hz,1H),4.26(dd,J=11.1,4.4Hz,1H); 13 C NMR (101MHz, D2O, 298K, δ): 162.6 (d, J = 244.5Hz), 132.2 (d, J = 3.2Hz), 128.9 (d, J = 8.6Hz), 115.4 (d, J = 21.8Hz), 78.0, 69.9; 19 F NMR (376MHz, D2O, 298K, δ): -113.92.

[0170] Experimental Example 37: Preparation of Sodium 2-Phenylacetane-1,2-Disulfate

[0171]

[0172] The experimental procedure is described in Example 31, using sodium 2-phenylpentane-1,2-disulfate (58%). 1 H-NMR yield). 1 H NMR (400MHz, CD3OD, 298K, δ): 7.47 (d, J = 7.5Hz, 2H), 7.31 (t, J = 7.6Hz, 2H), 7.21 (t, J = 7.3Hz, 1H), 4.17–4.11 (m, 2H),1.86(dtd,J=25.6,13.8,4.8Hz,2H),1.38–1.31(m,1H),1.04(dd,J=12.1,6.9Hz,1H),0.84(t,J=7.4Hz,3H); 13C NMR (101MHz, CD3OD, 298K, δ): 145.0, 128.9, 127.7, 126.8, 76.7, 75.8, 42.1, 17.4, 14.8.

[0173] Experimental Example 38: Preparation of Sodium 1-naphthylethane-1,2-disulfate

[0174]

[0175] The experimental procedure is described in Example 31, using sodium 1-naphthylethane-1,2-disulfate (53%). 1 H-NMR yield). 1 H NMR (400MHz, D2O, 298K, δ): 8.05–7.88 (m, 4H), 7.60 (ddd, J=9.9, 7.4, 2.4Hz, 3H), 5.7 9(dd,J=6.9,4.3Hz,1H), 4.46(dd,J=11.2,6.9Hz,1H), 4.39(dd,J=11.1,4.3Hz,1H); 13 C NMR (101MHz, D2O, 298K, δ): 133.8, 133.0, 132.7, 128.4, 128.1, 127.7, 126.7, 126.7, 126.6, 126.3, 124.24, 78.8, 70.0.

[0176] Experimental Example 39: Preparation of Sodium 1-(4-cyanophenyl)ethane-1,2-disulfate

[0177]

[0178] The experimental procedure is described in Example 31. Sodium 1-(4-cyanophenyl)ethane-1,2-disulfate (48%) 1 H-NMR yield). 1 H NMR (400MHz, D2O, 298K, δ): 7.86 (d, J = 8.4Hz, 2H), 7.68 (d, J = 8.4Hz, 2H), 5.68 (t, J = 5.2Hz, 1H), 4.40–4.30 (m, 2H); 13 C NMR (101MHz, D2O, 298K, δ): 142.0, 132.6, 127.5, 119.4, 111.2, 77.6, 69.6.

[0179] Experiment Example 40: Preparation of Sodium 1-(4-nitrophenyl)ethane-1,2-disulfate

[0180]

[0181] The experimental procedure is described in Example 31. Sodium 1-(4-nitrophenyl)ethane-1,2-disulfate (48%) 1 H-NMR yield). 1 H NMR (400MHz, D2O, 298K, δ): 8.45 (d, J = 8.6Hz, 2H), 7.88 (d, J = 8.6Hz, 2H), 5.88 (t, J = 4.8Hz, 1H), 4.56–4.46 (m, 2H); 13 C NMR (101MHz, D2O, 298K, δ): 147.7, 144.0, 128.0, 123.8, 77.5, 69.7.

[0182] Experiment Example 41: Preparation of Sodium 1-(6-chloropyridine-3-)ethane-1,2-disulfate

[0183]

[0184] The experimental procedure is described in Example 31. Sodium 1-(6-chloropyridine-3-)ethane-1,2-disulfate (48%) 1 H-NMR yield). 1 H NMR (400MHz, CD3OD, 298K, δ): 8.46 (d, J=2.0Hz, 1H), 7.94 (dd, J=8.4, 2.0Hz, 1H), 7.45 (d, J=8 .4Hz,1H),5.61(t,J=5.6Hz,1H),4.40(dd,J=10.8,5.2Hz,1H),4.24(dd,J=10.8,6.0Hz,1H); 13 C NMR (101MHz, CD3OD, 298K, δ): 151.5, 149.6, 139.9, 135.2, 125.1, 75.7, 70.0.

[0185] Experiment Example 42: Preparation of Sodium 2,3-Dihydrobenzofuran-2,3-Disulfate

[0186]

[0187] The experimental procedure is described in Example 31, using sodium 2,3-dihydrobenzofuran-2,3-disulfate (82%). 1 H-NMR yield). 1 HNMR (400MHz, D2O, 298K, δ): 7.65 (d, J = 7.5Hz, 1H), 7.50 (t, J = 7.8Hz, 1H), 7.19 (t, J = 7.5Hz, 1H), 7.11 (d, J = 8.2Hz, 1H), 6.48 (s, 1H), 5.76 (s, 1H); 13C NMR (101MHz, D2O, 298K, δ): 158.9, 132.4, 127.0, 123.0, 121.8, 111.2, 105.1, 81.6.

[0188] Experiment 40: Preparation of sodium disulfate, a tristyrosine derivative

[0189]

[0190] The experimental procedure is described in Example 31. The estrone derivative sodium disulfate (30%)... 1 H-NMR yield). 1 H NMR(400MHz,D2O,298K,δ):7.35(d,J=8.1Hz,1H),7.24(d,J=9.6Hz,2H),5.51 (dd,J=7.1,4.2Hz,1H),4.34–4.16(m,2H),2.86(t,J=9.2Hz,2H),2.55(dd,J= 19.6,8.2Hz,1H),2.41–2.33(m,1H),2.20(dt,J=19.2,8.3Hz,2H),2.11–1.92 (m,2H),1.88–1.81(m,1H),1.71–1.50(m,3H),1.48–1.28(m,3H),0.87(s,3H); 13 C NMR(101MHz,D2O,298K,δ):229.2,140.7,137.4,133.6,127.4,125.7,124.2,78 .6,70.0,52.2,49.7,48.6,43.6,37.5,36.0,30.9,28.7,25.8,25.1,21.1,13.3.

[0191] Experiment Example 44: Preparation of Sodium 1,1-diphenylethane-1,2-disulfate

[0192]

[0193] The experimental procedure is described in Example 31, using sodium 1,1-diphenylethane-1,2-disulfate (50%). 1 H-NMR yield). 1 H NMR (400MHz, CD3OD, 298K, δ): 7.45 (d, J = 7.5Hz, 4H), 7.29 (t, J = 7.6Hz, 4H), 7.21 (t, J = 7.3Hz, 2H), 4.52 (s, 2H); 13C NMR (101MHz, CD3OD, 298K, δ): 145.8, 128.9, 128.1, 127.9, 78.2, 74.3.

[0194] Experiment Example 45: Preparation of Sodium 1,1,2-triphenylethane-1,2-disulfate

[0195]

[0196] The experimental procedure is described in Example 31, using sodium 1,1,2-triphenylethane-1,2-disulfate (60%). 1 H-NMR yield). 1 HNMR (400MHz, CD3OD, 298K, δ): 7.71 (d, J=7.7Hz, 2H), 7.31 (t, J=7.6Hz, 2H), 7.2 1(t,J=7.3Hz,1H),7.14(dd,J=7.6,1.8Hz,2H),7.10–6.97(m,8H),6.14(s,1H); 13 C NMR (101MHz, CD3OD, 298K, δ): 146.7, 145.6, 138.4, 130.4, 128.9, 128.5, 128.2, 128.0, 127.9, 127.6, 127.3, 127.3, 84.9, 81.5.

[0197] Experiment Example 46: Preparation of Sodium Phenylacetonate-3-sulfate

[0198]

[0199] Styrene (0.2 mmol), cuprous oxide (0.02 mmol), ligand (0.02 mmol), potassium persulfate (0.2 mmol), tetrabutylpotassium persulfate (0.1 mmol), and trimethylsilyl cyanide (0.5 mmol) were added sequentially to a 4 mL reaction flask. After the additions, the 4 mL reaction flask was sealed and evacuated, then purged with argon gas. This process was repeated three times. Finally, 0.85 mL of dichloromethane and 0.15 mL of water were added to the flask, and the mixture was allowed to react at room temperature for 6 hours. After the reaction was complete, 200 mg of sodium bicarbonate was added to quench the reaction, and the organic phase was collected by filtration. The organic phase was concentrated and subjected to column chromatography. Tetrabutylammonium phenethylcyanide-3-sulfate was separated using a dichloromethane to methanol eluent with a volume ratio of 20:1. Finally, ion exchange was performed to obtain sodium phenethylcyanide-3-sulfate (91%). 1 H-NMR yield). 1H NMR (400MHz, CD3OD, 298K, δ): 7.48–7.33 (m, 5H), 4.49 (dd, J = 8.2, 5.7Hz, 1H), 4.28–4.18 (m, 2H); 13 C NMR (101MHz, CD3OD, 298K, δ): 132.4, 128.8, 128.3, 127.6, 119.0, 68.3, 37.4.

[0200] Experiment Example 47: Preparation of Sodium 1-(4-phenyl)phenethylcyano-3-sulfate

[0201]

[0202] The experimental procedure is described in Example 46, using sodium 1-(4-phenyl)phenethylcyano-3-sulfate (92%). 1 H-NMR yield). 1 H NMR (400MHz, CD3OD, 298K, δ): 7.67 (d, J = 8.4Hz, 2H), 7.62 (d, J = 8.3Hz, 2H), 7.53 (d, J = 7.9Hz, 2H),7.44(t,J=7.6Hz,2H),7.38–7.31(m,1H),4.55(dd,J=7.8,6.0Hz,1H),4.29–4.23(m,2H); 13 C NMR (101MHz, CD3OD, 298K, δ): 141.5, 140.1, 131.4, 128.5, 128.2, 127.3, 127.3, 126.6, 118.8, 68.2, 37.0.

[0203] Experiment Example 48: Preparation of Sodium p-fluorophenylacetonitrile-3-sulfate

[0204]

[0205] The experimental procedure is described in Example 46, using sodium fluorophenylacetonitrile-3-sulfate (90%). 1 H-NMR yield). 1 H NMR (400MHz, CD3OD, 298K, δ): 7.51 (dd, J=8.5, 5.2Hz, 2H), 7.17 (t, J=8.6Hz, 2H), 4.53 (dd, J=6.7Hz, 1H), 4.29–4.20 (m, 2H); 13 C NMR (101MHz, CD3OD, 298K, δ): 164.0, 161.5, 129.8, 129.7, 128.6, 128.6, 118.7, 115.7, 115.4, 68.1, 36.6.

[0206] Experiment Example 49: Preparation of Sodium p-Trifluoromethylphenylacetonitrile-3-sulfate

[0207]

[0208] The experimental procedure is described in Example 46, for sodium trifluoromethylphenylacetonitrile-3-sulfate (79%). 1 H-NMR yield). 1 H NMR (400MHz, D2O, 298K, δ): 7.66 (d, J = 10.3Hz, 2H), 7.53 (d, J = 10.2Hz, 2H), 4.56 (dd, J = 5.5Hz, 1H), 4.32–4.26 (m, 2H); 13 C NMR (101MHz, D2O, 298K, δ): 135.6, 130.3, 130.0, 128.6, 126.1, 126.1, 126.1, 126.0, 125.3, 122.6, 119.2, 68.2, 37.1; 19 F NMR (376MHz, D2O, 298K, δ): -62.52.

[0209] Experimental Example 50: Preparation of Sodium 3-acetoxyphenacetonitrile-3-sulfate

[0210]

[0211] The experimental procedure is described in Example 46, using sodium p-acetoxyphenacetonitrile-3-sulfate (87%). 1 H-NMR yield). 1 H NMR (400MHz, D2O, 298K, δ): 7.47 (d, J = 8.1Hz, 2H), 7.16 (d, J = 8.1Hz, 2H), 4.54 (dd, J = 6.3Hz, 1H), 4.43–4.20 (m, 2H), 2.31 (s, 3H); 13 C NMR (101MHz, D2O, 298K, δ): 173.2, 150.4, 129.7, 129.5, 122.5, 119.6, 68.4, 36.8, 20.5.

[0212] Experimental Example 51: Preparation of Sodium Methoxyphenylacetonitrile-3-sulfate

[0213]

[0214] The experimental procedure is described in Example 46, using sodium p-methoxyphenylacetonitrile-3-sulfate (45%). 1 H-NMR yield). 1H NMR (400MHz, D2O, 298K, δ): 7.41 (d, J = 8.5Hz, 2H), 7.03 (d, J = 8.5Hz, 2H), 4.49 (dd, J = 6.3Hz, 1H), 4.36–4.28 (m, 2H), 3.84 (s, 3H); 13 CNMR(101MHz,D2O,298K,δ):159.1,129.4,123.8,120.0,114.7,68.6,55.4,36.5.

[0215] Experimental Example 52: Preparation of Sodium p-tert-butylphenylacetonitrile-3-sulfate

[0216]

[0217] The experimental procedure is shown in Example 46, using sodium p-tert-butylphenylacetonitrile-3-sulfate (92%). 1 H-NMR yield). 1 H NMR (400MHz, CD3OD, 298K, δ): 7.48 (d, J = 8.1Hz, 2H), 7.38 (d, J = 8.1Hz, 2H), 4.47 (dd, J = 8.2, 5.8Hz, 1H), 4.23 (dd, J = 7.0, 5.0Hz, 2H), 1.34 (s, 9H); 13 C NMR (101MHz, CD3OD, 298K, δ): 151.5, 129.3, 127.3, 125.8, 119.0, 68.3, 37.0, 34.1, 30.3. Example 53: Preparation of sodium p-chlorophenylacetonitrile-3-sulfate.

[0218]

[0219] The experimental procedure is shown in Example 46, using sodium p-chlorophenylacetonitrile-3-sulfate (82%). 1 H-NMR yield). 1 H NMR (400MHz, D2O, 298K, δ): 7.51–7.36 (m, 4H), 4.55 (dd, J = 5.5Hz, 1H), 4.40–4.30 (m, 2H); 13 CNMR(101MHz,D2O,298K,δ):134.2,130.1,129.5,129.2,119.5,68.3,36.7.

[0220] Experimental Example 54: Preparation of Sodium m-chlorophenylacetonitrile-3-sulfate

[0221]

[0222] The experimental procedure is described in Example 46, using sodium m-chlorophenylacetonitrile-3-sulfate (89%). 1 H-NMR yield). 1 H NMR (400MHz, D2O, 298K, δ): 7.55–7.35 (m, 4H), 4.56 (dd, J = 7.1, 5.2Hz, 1H), 4.41–4.32 (m, 2H); 13 C NMR (101MHz, D2O, 298K, δ): 134.3, 133.4, 130.7, 129.0, 127.9, 126.4, 119.3, 68.2, 36.9.

[0223] Experimental Example 55: Preparation of Sodium α-methylphenacetonitrile-3-sulfate

[0224]

[0225] The experimental procedure is described in Example 46, using sodium α-methylphenacetonitrile-3-sulfate (88%). 1 H-NMR yield). 1 H NMR (400MHz, D2O, 298K, δ): 7.62–7.42 (m, 5H), 4.33 (q, J = 9.9Hz, 2H), 1.79 (s, 3H); 13 C NMR (101MHz, D2O, 298K, δ): 136.2, 129.3, 128.8, 126.0, 122.65, 72.4, 42.7, 22.5.

[0226] Experimental Example 56: Preparation of α-chlorobiphenyl-β-tetrabutylammonium sulfate

[0227]

[0228] Add bistyrene (0.1 mmol), cuprous chloride (0.01 mmol), ligand (0.01 mmol), potassium persulfate (0.1 mmol), tetrabutylpersulfate (0.05 mmol), and potassium chloride (0.3 mmol) sequentially to a 4 mL reaction flask. After addition, seal the 4 mL reaction flask, evacuate it, and then purge it with argon gas. Repeat this process three times. Finally, add 1.0 mL of dichloromethane to the flask and incubate at room temperature for 5 hours. After the reaction is complete, quench the reaction with 200 mg of sodium bicarbonate, and then filter to collect the organic phase. Concentrate the organic phase and perform column chromatography. Separate α-chlorobiphenyl-β-tetrabutylammonium sulfate (72%) using a dichloromethane to methanol eluent at a volume ratio of 20:1. 1 H-NMR yield). 1H NMR (400MHz, CDCl3, 298K, δ): 7.55 (dd, J=7.9, 3.9Hz, 5H), 7.50 (d, J=8.2Hz, 3H), 7.42 (t, J=7.6Hz, 2H), 7.33 (t, J=7.3Hz, 1H), 5.29 ( dd,J=8.2,5.8Hz,1H),4.43(dd,J=2.7Hz,1H),4.41(dd,J=1.8Hz,1H),1.64–1.58(m,8H),1.45–1.36(m,8H),0.97(t,J=7.3Hz,12H); 13 C NMR (101MHz, CDCl3, 298K, δ): 141.2, 140.5, 137.6, 128.7, 128.1, 127.4, 127.2, 127.0, 70.6, 60.7, 58.6, 23.9, 19.6, 13.6.

[0229] Experimental Example 57: Preparation of α-hydroxybiphenyl-β-tetrabutylammonium sulfate

[0230]

[0231] Add bistyrene (0.1 mmol), cuprous oxide (0.01 mmol), ligand (0.01 mmol), potassium persulfate (0.1 mmol), and tetrabutyl persulfate (0.05 mmol) sequentially to a 4 mL reaction flask. After the additions, seal the 4 mL reaction flask, evacuate it, and then purge it with argon gas. Repeat this process three times. Finally, add 0.9 mL of acetonitrile and 0.1 mL of water to the flask and incubate at room temperature for 4 hours. After the reaction is complete, quench the reaction with 200 mg of sodium bicarbonate, and then filter to collect the organic phase. Concentrate the organic phase and perform column chromatography. Separate α-hydroxybiphenyl-β-tetrabutylammonium sulfate (54%) using a dichloromethane to methanol eluent at a volume ratio of 20:1. 1 H-NMR yield). 1 H NMR (400MHz, CDCl3, 298K, δ): 7.53 (t, J = 8.1Hz, 4H), 7.45 (d, J = 8.2Hz, 2H), 7.39 (t, J = 7.6Hz, 2H), 7.29 (dd, J = 14.6, 7.3Hz, 1H), 5.03(dd,J=8.7,2.6Hz,1H),4.24–4.08(m,2H),3.29–3.11(m,8H),1.62–1.55(m,8H),1.43–1.31(m,8H),0.96(t,J=7.3Hz,12H); 13C NMR (101MHz, CDCl3, 298K, δ): 140.7, 140.1, 139.6, 128.6, 127.0, 126.8, 126.8, 126.7, 73.1, 58.4, 23.7, 19.5, 13.5.

[0232] Experimental Example 58: Preparation of α-azidobiphenyl-β-tetrabutylammonium sulfate

[0233]

[0234] Add bistyrene (0.2 mmol), copper trifluoroacetate hydrate (0.02 mmol), ligand (0.02 mmol), trimethyl azide (0.5 mmol), potassium persulfate (0.6 mmol), and tetrabutyl persulfate (0.1 mmol) sequentially to a 4 mL reaction flask. After the additions, seal the 4 mL reaction flask, evacuate it, and then purge it with argon gas. Repeat this process three times. Finally, add 1.0 mL of acetonitrile to the flask and incubate at room temperature for 15 hours. After the reaction is complete, quench the reaction with 200 mg of sodium bicarbonate, and then filter to collect the organic phase. Concentrate the organic phase and perform column chromatography. Separate α-azidobiphenyl-β-tetrabutylammonium sulfate (46%) using a dichloromethane to methanol eluent at a volume ratio of 20:1. 1 H-NMR yield). 1 H NMR (400MHz, CDCl3, 298K, δ): 7.35–7.16 (m, 5H), 4.89 (dd, J=9.1, 4.2Hz, 1H), 4.17 (dd, J=11.1, 4.2Hz, 1H ),4.04–3.98(m,1H),3.33–3.13(m,32H),1.60–1.52(m,32H),1.40–1.31(m,33H),0.91(t,J=7.3Hz,49H); 13 C NMR (101MHz, CDCl3, 298K, δ): 136.5, 128.4, 128.0, 126.9, 69.8, 64.7, 58.3, 23.7, 19.4, 13.4.

[0235] Experimental Example 59: Preparation of Tetrabutylammonium 3-Phenylacetylpropylsulfate

[0236]

[0237] Add (3-chloropropyl)benzene (0.2 mmol), cuprous bromide (0.02 mmol), ligand (0.02 mmol), tetrabutylammonium persulfate (0.6 mmol), pinacol diboronate (0.3 mmol), and lithium methoxide (0.6 mmol) sequentially to a 4 mL reaction flask. After the additions, seal the 4 mL reaction flask, evacuate it, and then purge it with argon gas. Repeat this process three times. Finally, add 2 mL of acetone to the flask and incubate the mixture at 60 °C for 18 hours. After the reaction is complete, filter and collect the organic phase. Concentrate the organic phase and perform column chromatography. Separate 3-phenyl-n-propyltetrabutylammonium sulfate (87%) using a dichloromethane to methanol eluent at a volume ratio of 20:1. 1 H-NMR yield). 1 H NMR (400MHz, CDCl3, 298K, δ): 7.03 (d, J=7.4Hz, 2H), 6.91–6.97 (m, 3H), 3.81 (t, J=6.6Hz, 2H), 3.02-3.06 (m, 8H),2.50(t,J=7.8Hz,2H),1.71-1.78(m,2H),1.36-1.44(m,8H),1.15-1.24(m,8H),0.76(t,J=7.4Hz,12H); 13 C NMR (101MHz, CDCl3, 298K, δ): 141.3, 127.8, 127.6, 125.1, 65.7, 57.8, 31.7, 30.9, 23.2, 19.0, 13.1.

[0238] Experimental Example 60: Preparation of Tetrabutylammonium 4-Alynylpentane Sulfate

[0239]

[0240] The experimental procedure is described in Example 59, 4-Alynylpentane tetrabutylammonium sulfate (84%). 1 H-NMR yield). 1 H NMR (400MHz, CDCl3, 298K, δ): 3.78 (t, J=6.3Hz, 2H), 3.00–3.04 (m, 8H), 3.78 (td, J=7.3, 2.6Hz, 2H), 1 .71(t,J=2.6Hz,1H),1.57–1.64(m,2H),1.35-1.43(m,8H),1.13–1.22(m,8H),0.73(t,J=7.3Hz,12H); 13 C NMR (101MHz, CDCl3, 298K, δ): 83.4, 68.0, 65.0, 57.9, 28.3, 23.3, 19.1, 14.7, 13.1.

[0241] Experimental Example: Preparation of Tetrabutylammonium Hexadecano-1-naphthylmethylsulfate

[0242]

[0243] The experimental procedure is described in Example 59, using naphthalene-1-ylmethylmethylammonium sulfate (84%). 1 H-NMR yield). 1 H NMR (400MHz, CDCl3, 298K, δ): 8.07–8.09 (m, 1H), 7.53–7.59 (m, 2H), 7.28 (d, J = 7.0Hz, 1H), 7.22–7.25 (m, 2H), 7.1 5(t,J=7.6Hz,1H),5.21(s,2H),2.70–2.74(m,8H),1.06-1.14(m,8H),0.94–1.03(m,8H),0.63(t,J=7.2Hz,12H); 13 CNMR (101MHz, CDCl3, 298K, δ): 132.9, 132.5, 131.3, 128.1, 127.7, 126.3, 125.6, 125.2, 124.6, 124.0, 66.5, 57.2, 22.8, 18.8, 13.0.

[0244] Experimental Example 62: Preparation of Tetrabutylammonium 2-(4-fluorophenyl)ethyl sulfate

[0245]

[0246] The experimental procedure is described in Example 59, 2-(4-fluorophenyl)ethyl tetrabutylammonium sulfate (87%). 1 H-NMR yield). 1 HNMR (400MHz, CDCl3, 298K, δ): 7.14-7.18 (m, 2H), 6.88 (t, J = 8.6Hz, 2H), 4.13 (t, J = 7.4Hz, 2H), 3.1 6-3.21(m,8H),2.92(t,J=7.3Hz,2H),1.52–1.60(m,8H),1.31–1.40(m,8H),0.93(t,J=7.3Hz,12H); 13 C NMR (101MHz, CDCl3, 298K, δ): 161.4 (d, J = 242.4Hz), 134.5 (d, J = 3.1Hz), 130.4 (d, J = 7.7Hz), 114.8 (d, J = 21Hz), 67.4, 58.6, 35.2, 23.9, 19.7, 13.7; 19FNMR (376MHz, CDCl3, 298K, δ): -117.6(m).

[0247] Experimental Example 63: Preparation of Tetrabutylammonium 2-Thienylethyl Sulfate

[0248]

[0249] The experimental procedure is described in Example 59, 2-thienylethyltetrabutylammonium sulfate (60%). 1 H-NMR yield). 1 H NMR (400MHz, CDCl3, 298K, δ): 7.07 (d, J=5.0Hz, 1H), 6.84–6.88 (m, 2H), 4.20 (t, J=7.4Hz ,2H),3.16–3.23(m,10H),1.55–1.63(m,8H),1.34–1.43(m,8H),0.96(t,J=7.3Hz,12H); 13 CNMR (101MHz, CDCl3, 298K, δ): 140.8, 126.7, 125.2, 123.3, 67.2, 58.6, 30.3, 23.9, 19.7, 13.7.

[0250] Experimental Example 64: Preparation of Tetrabutylammonium 4-(1-cyclohexyl-1H-tetrazole-5-yl)butylsulfate

[0251]

[0252] The experimental procedure is described in Example 59, 4-(1-cyclohexyl-1H-tetrazole-5-yl)butylsulfonate tetrabutylammonium (87%). 1 H-NMR yield). 1 H NMR (400MHz, CDCl3, 298K, δ): 4.09–4.17(m,1H),3.94(t,J=6.1Hz,2H),3.15–3.19(m,8H),2.78(t,J=7.7Hz,2H),1.77-1.86( m,8H),1.62–1.68(m,3H),1.50–1.58(m,8H),1.36–1.45(m,2H),1.25-1.34(m,8H),1.14–1.23(m,1H),0.85(t,J=7.4Hz,12H); 13 C NMR (101MHz, CDCl3, 298K, δ): 153.3, 64.9, 57.7, 56.3, 32.2, 27.8, 24.2, 24.1, 23.2, 23.0, 21.7, 18.8, 12.8.

[0253] Experimental Example 65: Preparation of Tetrabutylammonium Sulfate, a Caffeine Derivative

[0254]

[0255] The experimental procedure is described in Example 59, using tetrabutylammonium sulfate (55%), a caffeine derivative. 1 H-NMR yield). 1 H NMR (400MHz, CDCl3, 298K, δ):7.87–7.88(m,1H),4.64–4.66(m,2H),4.31–4.34(m,2H),3.54–3.55(m, 3H),3.35–3.36(m,3H),3.18–3.23(m,8H),1.56–1.62(m,8H),1.36–1.42(m,8H),0.94–0.98(m,12H); 13 C NMR (101MHz, CDCl3, 298K, δ): 155.4, 151.9, 148.9, 143.4, 106.5, 65.6, 58.8, 46.7, 29.8, 27.9, 24.0, 19.8, 13.7.

[0256] Experimental Example 66: Preparation of Tetrabutylammonium Sulfate, a Testosterone Derivative

[0257]

[0258] The experimental procedure is described in Example 59. Tetrabutylammonium sulfate (77%) is a testosterone derivative. 1 H-NMR yield). 1 HNMR (400MHz, CDCl3, 298K, δ): 5.67 (s, 1H), 4.53 (t, J = 8.3Hz, 2H), 4.00 (t, J = 6.1Hz, 2H), 3.22–3.26 (m, 8H), 1.89–2.44 (m, 12H), 1.71–1. 82(m,2H),1.57–1.65(m,10H),1.50–1.53(m,2H),1.34–1.45(m,8H),1.21–1.35(m,3H),1.15(s,3H),0.96(t,J=7.0Hz,12H),0.77(s,3H); 13C NMR (101MHz, CDCl3, 298K, δ): 199.5, 173.6, 171.2, 123.9, 82.3, 66.1, 58.7, 53.8, 50.3, 42.5, 38. 7,36.7,35.7,35.4,34.0,32.8,31.6,31.3,27.6,25.2,24.0,23.5,20.6,19.8,17.4,13.7,12.1.

[0259] Experimental Example 67: Preparation of Sodium Sulfate, an Adapalene Derivative

[0260]

[0261] The experimental procedure is described in Example 59. Tetrabutylammonium sulfate, a caffeine derivative, is used. Finally, ion exchange is performed to obtain sodium sulfate, an adapalene derivative (66%). 1 H-NMR yield). 1 H NMR (400MHz, DMSO-d6, 298K, δ): 8.64 (s, 1H), 8.23 ​​(s, 1H), 8.18 (d, J = 8.6Hz, 1H), 8.10(d,J=8.6Hz,1H),7.99(d,J=8.6Hz,1H),7.90(d,J=8.7Hz,1H),7.66(dd,J=8. 4,2.1Hz,1H),7.58(d,J=2.2Hz,1H),7.11(d,J=8.5Hz,1H),4.38(t,J=6.4Hz,2H) ,3.93(t,J=6.2Hz,2H),3.86(s,3H),2.13(s,6H),2.00–2.07(m,5H),1.75(s,6H); 13 C NMR(101MHz,DMSO-d6,298K,δ):165.9,158.6,140.4,138.1,135.6,131.4,130.9,130.3,129.9,1 28.6,126.7,126.1,125.8,125.1,125.1,124.1,112.7,32.5,62.1,55.4,36.6,36.6,28.6,28.4.

[0262] Experimental Example 68: Preparation of Febuxostat Derivative Sodium Sulfate

[0263]

[0264] The experimental procedure is described in Example 59. Febuxostat derivative tetrabutylammonium sulfate is used, and finally, ion exchange is performed to obtain febuxostat derivative sodium sulfate (86%). 1H-NMR yield). 1 H NMR (400MHz, CD3OD, 298K, δ): 8.21 (d, J = 2.2Hz, 1H), 8.17 (dd, J = 8.8, 2.3Hz, 1H), 7.27 (d, J = 8.8Hz, 1H), 4.42 (t ,J=6.2Hz,2H),4.17(t,J=6.1Hz,2H),3.99(d,J=6.4,2H),2.72(s,3H),2.09-2.22(m,3H),1.10(d,J=6.7,6H); 13 C NMR(101MHz,CD3OD,298K,δ):169.0,164.0,163.1,162.1,134.3,132.9,12 7.1,123.0,116.4,114.5,103.5,76.9,65.5,63.2,29.8,29.4,19.3,17.5.

[0265] Experimental Example 69: Preparation of Naproxen Derivative Sodium Sulfate

[0266]

[0267] The experimental procedure is described in Example 59. The naproxen derivative, tetrabutylammonium sulfate, is then subjected to ion exchange to obtain naproxen derivative sodium sulfate (97%). 1 H-NMR yield). 1 H NMR (400MHz, DMSO-d6, 298K, δ): 7.81(d,J=8.9Hz,1H),7.77(d,J=8.5Hz,1H),7.72(s,1H),7.39(d,J=8.4Hz,1H),7.28(d,J=2.4Hz,1H),7.14( dd,J=8.9,2.5Hz,1H),4.01-4.12(m,2H),3.91(q,J=7.1Hz,1H),3.86(s,3H),3.73(d,J=6.3Hz,2H),1.74-1.81(m,2H),1.47(d,J=7.0Hz,3H); 13 CNMR(101MHz,DMSO-d6,298K,δ):173.9,157.2,135.7,133.3,129.2,128. 4,127.0,126.2,125.5,118.7,105.7,62.2,61.6,55.1,44.4,28.5,18.5.

[0268] Experimental Example 70: Preparation of Fenofibrate Derivative Ammonium Sulfate

[0269]

[0270] The experimental procedure is described in Example 59, using fenofibrate derivative tetrabutylammonium sulfate (93%). 1 H-NMR yield). 1 HNMR (400MHz, CDCl3, 298K, δ): 7.65 (dd, J=8.6, 3.3Hz, 4H), 7.39 (d, J=8.2Hz, 2H), 6.79 (d, J=8.6Hz, 2H), 4.24 (t, J=6.5Hz, 2H ),3.97(t,J=6.1Hz,2H),3.16-3.20(m,8H),1.89-1.96(m,2H),1.52-1.59(m,14H),1.30-1.39(m,8H),0.91(t,J=7.2Hz,12H); 13 C NMR (101MHz, CDCl3, 298K, δ): 194.3, 173.5, 159.6, 138.2, 136.3, 132.0, 131. 2,130.2,128.5,117.4,79.4,63.3,63.0,58.6,28.8,25.4,23.9,19.6,13.6.

[0271] Experimental Example 71: Preparation of Ammonium Sulfate, a Flurbiprofen Derivative

[0272]

[0273] The experimental procedure is described in Example 59, using tetrabutylammonium sulfate (91%), a derivative of flurbiprofen. 1 H-NMR yield). 1 HNMR (400MHz, CDCl3, 298K, δ): 7.48 (d, J = 8.0Hz, 2H), 7.26-7.39 (m, 4H), 7.04-7.11 (m, 2H), 4.00-4.12 (m, 2H), 3.96 (t, J = 6.1Hz, 2 H),3.68(q,J=7.1Hz,1H),3.17-3.21(m,8H),1.53-1.74(m,12H),1.46(d,J=7.1Hz,3H),1.32-1.41(m,8H),0.93(t,J=7.3Hz,12H); 13C NMR (101MHz, CDCl3, 298K, δ): 173.9, 159.6 (d, J = 248.9Hz), 142.0 (d, J = 7.7Hz), 135.5, 130.7 (d, J = 4.0Hz), 128.9 (d, J = 3.0Hz), 128.4, 127.6 (d, J = 13.6Hz), 127.6, 123.6 (d, J = 3.3Hz), 115.1 (d, J = 23.7Hz), 66.2, 64.8, 58.6, 45.0, 45.0, 26.0, 25.2, 23.9, 19.6, 18.4, 13.6. Example 72: Preparation of ammonium sulfate, a celecoxib derivative.

[0274]

[0275] The experimental procedure is described in Example 59. The tetrabutylammonium sulfate derivative of cyclophosphamide (88%)... 1 H-NMR yield). 1 H NMR (400MHz, CDCl3, 298K, δ): 7.71 (d, J = 8.4Hz, 2H), 7.39 (d, J = 8.4Hz, 2H), 7.10 (d, J =7.9Hz,2H),7.03(d,J=7.9Hz,2H),6.66(s,1H),3.96(t,J=5.8Hz,2H),3.18-3.22(m ,8H),3.08(t,J=6.6Hz,2H),3.02(t,J=7.7Hz,2H),2.31(s,3H),1.54-1.62(m,12H), 1.31-1.43(m,10H),1.30-1.22(m,2H),0.92(t,J=7.4Hz,12H),0.80(t,J=7.3Hz,3H); 13 C NMR (101MHz, CDCl3, 298K, δ): 145.2, 143.8 (q, J = 38.6Hz), 142.1, 139.7, 139.6, 129.6, 128.6, 127.9, 125.6, 125.4, 121.0 (q, J = 270.1Hz), 106.1, 66.5, 58.6, 47.9, 47.9, 30.4, 26.7, 25.3, 23.8, 21.2, 19.8, 19.6, 13.6.

[0276] Experimental Example 73: Preparation of Ammonium Sulfate, an Isosorbide Derivative

[0277]

[0278] The experimental procedure is described in Example 59. The isocolic acid derivative, tetrabutylammonium sulfate (79%),1 H-NMR yield). 1 HNMR (400MHz, CDCl3, 298K, δ): 7.96 (d, J = 2.2Hz, 1H), 7.75 (d, J = 6.9Hz, 1H), 7.45 (td ,J=7.4,1.3Hz,1H),7.30–7.37(m,2H),7.26(t,J=3.7Hz,1H),6.90(d,J=8.4Hz,1H),5 .06(s,2H),4.00(t,J=6.2Hz,2H),3.91(t,J=6.1Hz,2H),3.50(s,2H),3.14-3.18(m, 8H),1.57–1.69(m,4H),1.49–1.55(m,8H),1.26–1.35(m,8H),0.87(t,J=7.3Hz,12H); 13 C NMR (101MHz, CDCl3, 298K, δ): 190.5, 171.2, 160.2, 140.1, 136.2, 135.5, 132.7, 132.1, 129.1, 129.0,127.7,127.7,124.9,120.9,73.4,66.0,64.6,58.4,40.0,25.9,25.0,23.7,19.5,13.5.

[0279] Experimental Example 74: Preparation of Sodium 2-Phenylon-1-Ethyl Sulfate

[0280]

[0281] Add 0.2 mmol of 2-phenyl-1-ethylboronate, 0.4 mmol of ammonium persulfate, 0.24 mmol of tetrabutylammonium hydrogen sulfate, and 0.2 mmol of sodium fluoride sequentially to a 4 mL reaction flask. After the additions, seal the 4 mL reaction flask, evacuate it, and then purge it with argon gas. Repeat this process three times. Finally, add 1 mL of tetrahydrofuran to the flask and allow it to react at room temperature for 12 hours. After the reaction is complete, quench the reaction with sodium bicarbonate, and then collect the organic phase. Concentrate the organic phase and perform column chromatography. Separate 2-phenyl-1-ethylammonium hydrogen sulfate using a dichloromethane to methanol eluent with a volume ratio of 20:1. Finally, perform ion exchange to obtain sodium 2-phenyl-1-ethylammonium sulfate (86%). 1 H-NMR yield). 1 H NMR (400MHz, D2O, 298K, δ): 7.38 (dq, J=15.6, 7.7Hz, 5H), 4.29 (t, J=6.6Hz, 2H), 3.03 (t, J=6.6Hz, 2H); 13C NMR (101MHz, D2O, 298K, δ): 138.0, 129.1, 128.7, 126.7, 69.5, 34.8.

[0282] Experimental Example 75: Preparation of Sodium 2-(4-tert-butylphenyl)-1-ethyl sulfate

[0283]

[0284] The experimental procedure is described in Example 74, using sodium 2-(4-tert-butylbenzene)-1-ethyl sulfate (72%). 1 H-NMR yield). 1 HNMR (400MHz, CD3OD, 298K, δ): 7.30 (d, J = 8.3Hz, 2H), 7.18 (d, J = 8.3Hz, 2H), 4.18 (t, J = 7.2Hz, 2H), 2.94 (t, J = 7.2Hz, 2H), 1.29 (s, 9H); 13 C NMR (101MHz, CD3OD, 298K, δ): 150.2, 36.1, 129.6, 126.2, 9.7, 36.2, 5.1, 31.8

[0285] Experimental Example 76: Preparation of Sodium 2-(4-methoxycarbonylbenzene)-1-ethyl sulfate

[0286]

[0287] The experimental procedure is described in Example 74, using sodium 2-(4-methoxycarbonylbenzene)-1-ethyl sulfate (71%). 1 H-NMR yield). 1 HNMR (400MHz, CD3OD, 298K, δ): 7.97–7.91 (m, 2H), 7.43–7.38 (m, 2H), 4.23 (t, J = 6.8Hz, 2H), 3.89 (s, 3H), 3.06 (t, J = 6.8Hz, 2H); 13 C NMR (101MHz, CD3OD, 298K, δ): 168.4 145.4 130.4, 130.1, 129.2, 68.7, 52.3, 36.4.

[0288] Experimental Example 77: Preparation of Sodium 2-(4-chlorobenzene)-1-ethyl sulfate

[0289]

[0290] The experimental procedure is described in Example 74, using sodium 2-(4-chlorobenzene)-1-ethyl sulfate (72%). 1 H-NMR yield). 1H NMR (400MHz, D2O, 298K, δ): 7.36 (d, J = 8.2Hz, 2H), 7.28 (d, J = 8.2Hz, 2H), 4.25 (t, J = 6.5Hz, 2H), 2.98 (t, J = 6.5Hz, 2H); 13 C NMR (101MHz, D2O, 298K, δ): 136.6, 131.7, 130.5, 128.4, 69.2, 34.1.

[0291] Experimental Example 78: Preparation of Sodium 2-(2-chlorobenzene)-1-ethyl sulfate

[0292]

[0293] The experimental procedure is described in Example 74, using sodium 2-(2-chlorobenzene)-1-ethyl sulfate (80%). 1 H-NMR yield). 1 H NMR (400MHz, D2O, 298K, δ): 7.44 (d, J = 7.3Hz, 1H), 7.37 (d, J = 7.3Hz, 1H), 7.28 (p, J = 7.3Hz, 2H), 4.29 (t, J = 6.6Hz, 2H), 3.14 (t, J = 6.7Hz, 2H); 13 C NMR (101MHz, D2O, 298K, δ): 135.0, 133.6, 131.4, 129.4, 128.4, 127.1, 67.8, 32.7.

[0294] Experimental Example 79: Preparation of Sodium 2,2-Diphenyl-1-ethylsulfate

[0295]

[0296] The experimental procedure is described in Example 74, using sodium 2,2-diphenyl-1-ethyl sulfate (27%). 1 H-NMR yield). 1 H NMR (400MHz, D2O, 298K, δ): 7.38 (d, J = 4.3Hz, 8H), 7.30 (h, J = 4.3Hz, 2H), 4.61 (d, J = 7.6Hz, 2H), 4.47 (t, J = 7.6Hz, 1H); 13 C NMR (101MHz, D2O, 298K, δ): 141.0, 128.9, 128.1, 127.1, 70.4, 49.8.

[0297] Experimental Example 80: Preparation of Sodium 4-(4-biphenoxy)-1-butylsulfate

[0298]

[0299] The experimental procedure is described in Example 74, using sodium 4-(4-biphenoxy)-1-butyl sulfate (80%). 1 H-NMR yield). 1 HNMR (400MHz, DMSO-d6, 298K, δ): 7.64–7.55 (m, 4H), 7.42 (t, J = 7.7Hz, 2H), 7.30 (t, J = 7.4Hz, 1H), 7. 05–6.99(m,2H),4.02(t,J=6.4Hz,2H),3.77(t,J=6.4Hz,2H),1.81–1.72(m,2H),1.71–1.62(m,2H); 13 C NMR (101MHz, DMSO-d6, 298K, δ): 158.3, 139.9, 132.4, 128.8, 127.8, 126.6, 126.2, 114.9, 67.2, 65.1, 25.7, 25.5.

[0300] Experimental Example 81: Preparation of Sodium 4-Carbazole-1-Butylsulfate

[0301]

[0302] The experimental procedure is described in Example 74, 4-carbazole-1-butylsulfate sodium (63%, 85.8 mg). 1 H NMR(400MHz, CD3OD, 298K, δ):8.04(d,J=7.7Hz,2H),7.46(d,J=8.2Hz,2H),7.43–7.37(m,2H),7.19– 7.13(m,2H),4.35(t,J=7.2Hz,2H),4.02(t,J=6.3Hz,2H),1.94(p,J=7.1Hz,2H),1.72–1.63(m,2H); 13 C NMR (101MHz, CD3OD, 298K, δ): 141.6, 126.6, 124.0, 121.0, 119.7, 109.9, 68.7, 43.1, 27.8, 26.5.

[0303] Experimental Example 82: Preparation of Sodium 3-((thiophene-2-carbonyl)oxy)-1-propyl sulfate

[0304]

[0305] The experimental procedure is described in Example 74, using sodium 3-((thiophene-2-carbonyl)oxy)-1-propyl sulfate (81%). 1 H-NMR yield).1 H NMR (400MHz, CD3OD, 298K, δ): 7.82 (d, J = 3.7Hz, 1H), 7.75 (d, J = 5.0Hz, 1H), 7.15 (t ,J=4.4Hz,1H),4.40(t,J=6.4Hz,2H),4.17(t,J=6.2Hz,2H),2.11(p,J=6.3Hz,2H); 13 C NMR (101MHz, CD3OD, 298K, δ): 163.7, 134.7, 134.5, 134.1, 129.0, 65.6, 63.0, 29.8.

[0306] Experimental Example 83: Preparation of 3-((quinoline-2-carbonyl)oxy)propyl-1-tetrabutylammonium sulfate

[0307]

[0308] The experimental procedure is described in Example 74, 3-((quinoline-2-carbonyl)oxy)propyl-1-tetrabutylammonium sulfate (57%). 1 H-NMR yield). 1 H NMR (400MHz, CDCl3, 298K, δ): 8.25 (d, J = 8.6 Hz, 2H), 8.11 ( d, J = 8.5 Hz, 1H), 7.83 ( d, J = 8.2 Hz, 1H), 7.73 ( t, J = 7.8 Hz, 1H), 7.59 ( t, J = 7.6 Hz, 1H), 4.57 ( t,J=6.7Hz,2H),4.21(t,J=6.3Hz,2H),3.33–3.17(m,8H),2.20(p,J=6.6Hz ,2H),1.61(p,J=7.7Hz,8H),1.39(h,J=7.3Hz,8H),0.95(t,J=7.3Hz,12H); 13 C NMR (101MHz, CDCl3, 298K, δ): 165.2, 148.2, 147.7, 137.3, 130.8, 130.2, 129.3, 128.6, 127.6, 121.2, 63.9, 63.6, 58.8, 29.1, 24.0, 19.8, 13.7.

[0309] Experimental Example 84: Preparation of 4-(4-(methylsulfonyl)phenoxy)butyl-1-tetrabutylammonium sulfate

[0310]

[0311] The experimental procedure is described in Example 74, 4-(4-(methylsulfonyl)phenoxy)butyl-1-tetrabutylammonium sulfate (83%).1 H-NMR yield). 1 H NMR (400MHz, CDCl3, 298K, δ): 7.81–7.72 (m, 2H), 7.01–6.92 (m, 2H), 4.03 (t, J = 6.3Hz, 4H), 3.25–3.16 (m, 8H), 2.97 (s, 3H), 1.89 (p, J = 6.7Hz, 2H), 1.79 (h, J = 6.9Hz, 2H), 1.58 (p, J = 7.8Hz, 8H), 1.37 (h, J = 7.4Hz, 9H), 0.93 (t, J = 7.3Hz, 12H); 13 C NMR (101MHz, CDCl3, 298K, δ): 163.3, 131.8, 129.4, 115.1, 68.2, 66.3, 58.7, 44.9, 25.9, 25.6, 23.9, 19.7, 13.7.

[0312] Experimental Example 85: Preparation of Tetrabutylammonium Sulfate, a 4-methylcoumarin Derivative

[0313]

[0314] The experimental procedure is described in Example 74, 4-methylcoumarin derivative tetrabutylammonium sulfate (67%). 1 H-NMR yield). 1 H NMR (400MHz, CDCl3, 298K, δ): 7.42 (d, J=8.8Hz, 1H), 6.78 (dd, J=8.8, 2.4Hz, 1H), 6.68 (d, J=2.4Hz, 1H), 6.01 (s, 1H), 4.05–3.94 (m, 4H), 3.27–3.17 (m ,8H),2.32(s,3H),1.87(dq,J=11.7,6.6Hz,2H),1.82–1.72(m,2H),1.58(t d,J=11.6,10.1,6.0Hz,8H),1.37(h,J=7.3Hz,8H),0.92(t,J=7.3Hz,13H); 13 C NMR (101MHz, CDCl3, 298K, δ): 162.2,161.3,155.1,152.8,125.6,113.3,1 12.4,111.5,101.4,68.2,66.3,58.6,26.0,25.6,23.9,19.6,18.6,13.6.

[0315] Experimental Example 86: Preparation of Sodium 1-Tolylpiperidine-4-Sulfate

[0316]

[0317] The experimental procedure is described in Example 74, 1-Tolylpiperidine-4-sulfate sodium (41%, 58.3 mg). 1 H NMR (400MHz, CD3OD, 298K, δ): 7.65 (d, J = 8.0Hz, 2H), 7.42 (d, J = 7.9Hz, 2H), 4.41 (td, J = 5.8 ,2.8Hz,1H),3.07(dtt,J=19.8,7.9,4.8Hz,4H),2.45(s,3H),1.93(tt,J=7.5,3.3Hz,4H); 13 C NMR (101MHz, CD3OD, 298K, δ): 145.3, 134.4, 130.8, 128.8, 73.2, 44.0, 31.8, 21.5.

[0318] Experimental Example 87: Preparation of Naproxen Derivative Sodium Sulfate

[0319]

[0320] The experimental procedure is described in Example 74. Naproxen derivative sodium sulfate (67%) 1 H-NMR yield). 1 H NMR (400MHz, CD3OD, 298K, δ): 7.73 (dd, J=8.7, 3.4Hz, 2H), 7.69–7.64 (m, 1H), 7.39 (dd, J=8.6, 1.8Hz, 1H), 7.20 (d, J=2.5Hz, 1H), 7.11 (d d,J=9.0,2.5Hz,1H),4.20(dt,J=9.0,6.2Hz,2H),4.02(t,J=6.3Hz,2H),3.90(s,3H),1.94(td,J=6.3,1.5Hz,2H),1.55(d,J=7.2Hz,3H); 13 C NMR (101MHz, CD3OD, 298K, δ): 176.4, 159.1, 137.0, 135.2, 130.4, 130.2, 128.2, 127.1, 126.9, 119.9, 106.6, 65.5, 62.6, 55.7, 46.6, 29.7, 18.9.

[0321] Experimental Example 88: Preparation of febuxostat derivative ammonium sulfate

[0322]

[0323] The experimental procedure is described in Example 74, using febuxostat derivative tetrabutylammonium sulfate (66%).1 H-NMR yield). 1 HNMR (400MHz, CDCl3, 298K, δ): 8.13 (s, 1H), 8.03 (d, J = 8.9 Hz, 1H), 6.99 (d, J = 8.9 Hz,1H),4.38(t,J=6.4Hz,2H),4.14(t,J=6.2Hz,2H),3.86(d,J=6.4Hz,2H),3.29 –3.19(m,8H),2.69(s,3H),2.12(dp,J=26.4,6.5Hz,3H),1.61(td,J=12.0,10.2, 6.0Hz, 8H), 1.40 (h, J = 7.4Hz, 8H), 1.04 (d, J = 6.7Hz, 6H), 0.96 (t, J = 7.3Hz, 12H); 13 C NMR (101MHz, CDCl3, 298K, δ):167.2,162.5,162.0,161.0,132.7,131.9,126.1,122.0, 115.5,112.8,102.8,75.7,63.5,62.7,58.7,29.1,28.2,24.0,19.7,19.0,17.5,13.7.

[0324] Experimental Example 89: Preparation of Sodium 3-Phenylacetic Acid

[0325]

[0326] Add 0.2 mmol of 3-phenyl-1-propanol, 0.4 mmol of potassium persulfate, and 0.24 mmol of tetrabutylammonium hydrogen sulfate sequentially to a 4 mL reaction flask. After the additions are complete, seal the 4 mL reaction flask, evacuate it, and then purge it with argon gas. Repeat this process three times. Finally, add 1 mL of N,N-dimethylformamide to the flask and react at 80 °C for 12 hours. After the reaction is complete, add water and dichloromethane to quench the reaction, and then collect the organic phase. Concentrate the organic phase and perform column chromatography. Separate 3-phenylpropylammonium hydrogen sulfate using a dichloromethane to methanol eluent with a volume ratio of 20:1 (dichloromethane to methanol). Finally, perform ion exchange to obtain sodium 3-phenylpropylammonium sulfate (97%). 1 H-NMR yield). 1 H NMR (400MHz, CD3OD, 298K, δ): 7.27-7.20 (m, 4H), 7.16-7.13 (m, 1H), 4.01 (t, J = 6.4Hz, 2H), 2.72 (t, J = 7.7Hz, 2H), 1.99-1.90 (m, 2H); 13C NMR (101MHz, CD3OD, 298K, δ): 142.9, 129.5, 129.3, 126.8, 68.3, 33.0, 32.4.

[0327] Experimental Example 90: Preparation of Sodium 2-(4-hydroxyphenyl)ethyl sulfate

[0328]

[0329] The experimental procedure is described in Example 89. Sodium 2-(4-hydroxyphenyl)ethyl sulfate (78%) 1 H-NMR yield). 1 H NMR (400MHz, D2O, 298K, δ): 7.23 (d, J = 8.5Hz, 2H), 6.89 (d, J = 8.5Hz, 2H), 4.25 (t, J = 6.7Hz, 2H), 2.95 (t, J = 6.7Hz, 2H); 13 C NMR (101MHz, D2O, 298K, δ): 154.0, 130.3, 129.8, 115.4, 69.7, 33.9.

[0330] Experimental Example 91: Preparation of Sodium 4-pentene-1-sulfate

[0331]

[0332] The experimental procedure is described in Example 89, 4-pentene-1-tetrabutylammonium sulfate (82%). 1 H-NMR yield). 1 H NMR (400MHz, CD3OD, 298K, δ): 5.90-5.80 (m, 1H), 5.05 (dd, J=17.1, 1.8Hz, 1H), 4.97 (d, J=10.3Hz, 1H), 3.99 (t, J=6.5Hz, 2H) ,3.27-3.23(m,8H),2.19-2.14(m,2H),1.78-1.73(m,2H),1.71-1.63(m,8H),1.42(h,J=7.4Hz,8H),1.02(t,J=7.4Hz,12H); 13 C NMR (101MHz, CD3OD, 298K, δ): 139.0, 115.5, 68.1, 59.43, 59.40, 59.37, 31.0, 29.8, 24.7, 20.65, 20.63, 20.62, 14.0.

[0333] Experimental Example 92: Preparation of Sodium (E)-3-phenylprop-2-ene-1-sulfate

[0334]

[0335] The experimental procedure is described in Example 89, (E)-3-phenylprop-2-ene-1-tetrabutylammonium sulfate (30%). 1 H-NMR yield). 1 H NMR (400MHz, CD3OD, 298K, δ): 7.42 (d, J = 7.2Hz, 2H), 7.32 (t, J = 7.5Hz, 2H), 7.24 (t, J = 7.3Hz, 1H), 6.68 (d, J = 15.9Hz, 1H), 6.39 (d t,J=15.9,6.2Hz,1H),4.65(d,J=6.5Hz,2H),3.22-3.18(m,8H),1.65-1.59(m,8H),1.40(h,J=7.4Hz,8H),1.00(t,J=7.4Hz,12H); 13 C NMR (101MHz, CD3OD, 298K, δ): 137.8, 134.0, 129.6, 128.9, 127.5, 125.5, 69.3, 59.3, 24.7, 20.6, 14.0.

[0336] Experimental Example 93: Preparation of Sodium 4-pentyne-1-sulfate

[0337]

[0338] The experimental procedure is described in Example 89, using sodium 4-pentyne-1-sulfate (79%). 1 H-NMR yield). 1 H NMR (400MHz, D2O, 298K, δ): 4.21 (t, J = 6.1 Hz, 2H), 2.39 (t, J = 7.0 Hz, 2H), 1.95 (p, J = 6.6 Hz, 2H); 13 CNMR(101MHz,CD3OD,298K,δ):84.0,69.9,67.6,29.7,15.6.

[0339] Experimental Example 94: Preparation of Sodium 3-Phenylacetyl-1-sulfate

[0340]

[0341] The experimental procedure is described in Example 89, sodium 3-phenylprop-2-yne-1-sulfate (47%). 1 H-NMR yield). 1 H NMR(400MHz,D2O,298K,δ):7.60-7.58(m,2H),7.50-7.44(m,3H),4.96(s,2H);13 C NMR (101MHz, D2O, 298K, δ): 131.8, 129.3, 128.6, 121.4, 87.3, 83.0, 57.1.

[0342] Experimental Example 95: Preparation of Sodium Cyclopropylmethylsulfate

[0343]

[0344] The experimental procedure is described in Example 89, using sodium cyclopropyl methyl sulfate (69%). 1 H-NMR yield). 1 H NMR (400MHz, CD3OD, 298K, δ): 3.82 (d, J = 7.2Hz, 2H), 1.20-1.10 (m, 1H), 0.58-0.53 (m, 2H), 0.31-0.27 (m, 2H); 13 C NMR (101MHz, CD3OD, 298K, δ): 74.0, 11.1, 3.6.

[0345] Experimental Example 96: Preparation of Sodium 2-(thiophen-3-yl)ethane-1-sulfate

[0346]

[0347] The experimental procedure is described in Example 89, using sodium 2-(thiophen-3-yl)ethane-1-sulfate (77%). 1 H-NMR yield). 1 HNMR (400MHz, CD3OD, 298K, δ): 7.30 (dd, J = 5.0, 3.0Hz, 1H), 7.15 (s, 1H), 7.03 (d, J = 4.9Hz, 1H), 4.19 (t, J = 7.0Hz, 2H), 3.01 (t, J = 7.0Hz, 2H); 13 C NMR (101MHz, CD3OD, 298K, δ): 139.6, 129.4, 126.2, 122.4, 69.0, 31.2.

[0348] Experimental Example 97: Preparation of Sodium 2-(4-methylthiazolyl-5-yl)ethane-1-sulfate

[0349]

[0350] The experimental procedure is described in Example 89, 2-(4-methylthiazolyl-5-yl)ethane-1-tetrabutylammonium sulfate (77%). 1 H-NMR yield). 1H NMR (400MHz, CD3OD, 298K, δ): 8.76 (s, 1H), 4.15 (t, J = 6.5Hz, 2H), 3.26-3.22 (m, 8H), 3.18 (t, J=6.5Hz,2H),2.40(s,3H),1.70-1.62(m,8H),1.41(h,J=7.4Hz,8H),1.02(t,J=7.4Hz,12H); 13 C NMR (101MHz, CD3OD, 298K, δ): 152.3, 150.4, 129.3, 68.5, 59.5, 27.4, 24.8, 20.7, 14.6, 14.0.

[0351] Experimental Example 98: Preparation of Sodium Adamantane Sulfate

[0352]

[0353] The experimental procedure is described in Example 89, sodium 2-adamantane sulfate (98%). 1 H-NMR yield). 1 H NMR (400MHz, CD3OD, 298K, δ): 4.51 (t, J = 3.2Hz, 1H), 2.15 (d, J = 13.6Hz, 4H), 1.91-1.87 (m, 2H), 1.78 (d, J = 9.4Hz, 6H), 1.55 (d, J = 13.1Hz, 2H); 13 C NMR (101MHz, CD3OD, 298K, δ): 83.1, 38.6, 37.6, 34.0, 32.4, 28.6, 28.4.

[0354] Experimental Example 99: Preparation of Sodium α-formic acid-4-fluorobenzyl sulfate

[0355]

[0356] The experimental procedure is described in Example 89, sodium α-formic acid-4-fluorobenzyl sulfate (87%). 1 H-NMR yield). 1 H NMR (400MHz, CD3OD, 298K, δ): 7.54 (dd, J=8.6, 5.5Hz, 2H), 7.10 (t, J=8.7Hz, 2H), 5.67 (s, 1H),3.24-3.20(m,8H),1.67-1.59(m,8H),1.39(h,J=7.4Hz,8H),0.98(t,J=7.4Hz,12H); 13C NMR (101MHz, CD3OD, 298K, δ): 173.2, 165.2, 162.8, 134.0, 134.0, 130.4, 130.3, 116.1, 115.9, 78.0, 59.3, 24.6, 20.5, 14.0; 19 F NMR (376MHz, CD3OD, 298K, δ): -115.20. Experimental Example 100: Preparation of DL-pantolactone sodium sulfate.

[0357]

[0358] The experimental procedure is described in Example 89, DL-pantolactone tetrabutylammonium sulfate (73%). 1 H-NMR yield). 1 H NMR(400MHz,CD3OD,298K,δ):4.84(s,1H),4.06-4.01(m,2H),3.28-3.24(m,8H),1.71 -1.63(m,8H),1.42(h,J=7.4Hz,8H),1.29(s,3H),1.10(s,3H),1.02(t,J=7.4Hz,12H); 13 C NMR (101MHz, CD3OD, 298K, δ): 175.4, 80.6, 77.1, 59.4, 41.5, 24.8, 23.1, 20.6, 19.8, 14.0.

[0359] Experimental Example 101: Preparation of Sodium Icaridin Sulfate

[0360]

[0361] The experimental procedure is described in Example 89, using tetrabutylammonium iodide sulfate (43%). 1 H-NMR yield). 1 H NMR (400MHz, CD3OD, 298K, δ): 4.69 (h, J = 6.2Hz, 1H), 4.43-4.38 (m, 1H), 4.02-3.95 (m, 3H), 3.27-3.23 (m, 8H), 2.96-2.88 (m, 1H), 2.17-2.06 (m ,1H),1.96-1.86(m,1H),1.71-1.59(m,15H),1.42(h,J=7.4Hz,9H),1.2 2(t,J=6.8Hz,3H),1.02(t,J=7.3Hz,12H),0.92(td,J=7.5,3.8Hz,3H); 13C NMR(101MHz,CD3OD,298K,δ):157.14,157.11,74.7,66.6,59.5,49.6,49.6,40.1,40.0,30.6 ,30.04,30.01,29.4,26.7,26.6,24.8,20.70,20.68,20.66,20.1,19.9,14.0,10.14,10.07.

[0362] Example 102: Preparation of Sodium Hydroxypropyl Theophylline Sulfate

[0363]

[0364] The experimental procedure is described in Example 89. Hydroxypropyltheophylline sodium sulfate (80%) 1 H-NMR yield). 1 H NMR (400MHz, CD3OD, 298K, δ): 7.93 (s, 1H), 4.81-4.76 (m, 1H), 4.57 (dd, J=14.2, 3.0H z,1H),4.37(dd,J=14.2,7.7Hz,1H),3.53(s,3H),3.34(s,3H),1.34(d,J=6.5Hz,3H); 13 C NMR (101MHz, CD3OD, 298K, δ): 156.7, 153.3, 149.8, 144.6, 108.4, 74.7, 52.2, 30.2, 28.3, 18.2.

[0365] Experimental Example 103: Preparation of Sodium Diosgenin Sulfate

[0366]

[0367] The experimental procedure is described in Example 89. Diosgenin sodium sulfate (65%) 1 H-NMR yield). 1 H NMR(400MHz,CD3OD,298K,δ):5.40-5.39(m,1H),4.43-4.37(m,1H),4.18-4.10(m,1H),3.47-3.42(m,1H),2.57-2.52(m,1H),2.38-2.31(m,1H), 2.05-1.99(m,4H),1.92-1.87(m,3H),1.77-1.73(m,3H),1.68-1.54(m, 9H),1.29(s,3H),1.05(s,4H),0.96(d,J=6.9Hz,4H),0.82-0.78(m,5H); 13C NMR (101MHz, CD3OD, 298K, δ): 141.6, 123.0, 110.6, 82.2, 79.7, 67.8, 63.7, 57.7, 51.6, 42.9, 41. 4,40.9,40.4,38.4,37.8,33.2,32.8,32.7,32.4,31.4,30.0,29.9,22.0,19.8,17.5,16.8,14.9.

[0368] Experimental Example 104: Preparation of 1-(4-biphenyl)-1,3-butanedione-α-sulfuric acid

[0369]

[0370] Add 0.2 mmol of 1-(4-biphenyl)-1,3-butanedione, 0.01 mmol of silver nitrate, 0.03 mmol of ligand, 0.6 mmol of potassium persulfate, and 0.12 mmol of tetrabutylammonium persulfate sequentially to a 4 mL reaction flask. After the additions, seal the 4 mL reaction flask, evacuate it, and then purge it with argon gas. Repeat this process three times. Finally, add 1.5 mL of dichloromethane to the flask and react at 50 °C for 18 hours. After the reaction is complete, quench the reaction with 200 mg of sodium bicarbonate, and then filter to collect the organic phase. Concentrate the organic phase and perform column chromatography. Separate 1-(4-biphenyl)-1,3-butanedione-α-tetrabutylammonium sulfate (88%) using a dichloromethane to methanol eluent at a volume ratio of 20:1. 1 H-NMR yield). 1 H NMR (400MHz, CDCl3, 298K, δ): 15.48* (s, 0.1H), 8.32* (d, J=8.3Hz, 0.2H), 8.19 (d,J=8.3Hz,2H),7.64(d,J=8.5Hz,2H),7.58(d,J=7.2Hz,2H),7.44(t,J=7.4H z,2H),7.37(t,J=7.3Hz,1H),5.87(s,1H),3.19–3.15(m,9H),2.50*(s,0.3H), 2.39(s,3H),1.61-1.53(m,9H),1.36(h,J=7.3Hz,9H),0.93(t,J=7.2Hz,13H); 13C NMR (101MHz, CDCl3, 298K, δ): 205.6,193.2,146.0,139.7,133.6,130.2,130.1*,128 .9,128.8*,128.2,127.1,127.0,126.9*,126.2*,83.2,58.4,26.8,23.7,19.5,13.5.

[0371] Experimental Example 105: Preparation of 1-(4-bromobenzene)-1,3-butanedione-α-sulfuric acid

[0372]

[0373] The experimental procedure is described in Example 104, 1-(4-bromobenzene)-1,3-butanedione-α-tetrabutylammonium sulfate (93%). 1 H-NMR yield). 1 H NMR (400MHz, CDCl3, 298K, δ): 15.30*(s,0.3H),8.07*(d,J=8.3Hz,0.5H),7.99(d,J=8.3Hz,2H),7.55(d,J=8.2Hz,2H),7.46*(d,J=8.4 Hz,0.5H),5.75(s,1H),3.17-3.13(m,10H),2.47*(s,0.8H),2.36(s,3H),1.57(s,10H),1.36(q,J=7.2Hz,10H),0.95(t,J=6.8Hz,15H); 13 C NMR (101MHz, CDCl3, 298K, δ): 205.3,196.0*,193,173.1*,133.7,131.7,131.2,1 31.1*,130.8*,130.2*,128.8,125.3*,83.2,58.4,26.8,23.8,23.6*,19.6,13.6.

[0374] Experimental Example 106: Preparation of 1-(4-methoxybenzene)-1,3-butanedione-α-sulfuric acid

[0375]

[0376] The experimental procedure is described in Example 104, 1-(4-methoxybenzene)-1,3-butanedione-α-tetrabutylammonium sulfate (74%). 1 H-NMR yield). 1H NMR (400MHz, CDCl3, 298K, δ): 15.67*(s,0.06H),8.26(d,J=9.0Hz,0.1H),8.12(d,J=8.9Hz,2H),6.89(d,J=9.0Hz,2H),5.80(s,1H),3.83 (s,3H),3.80*(s,0.2H),3.20–3.16(m,8H),2.44(s,0.2H),2.35(s,3H),1.62–1.54(m,8H),1.36(h,J=7.3Hz,8H),0.94(t,J=7.3Hz,13H); 13 C NMR (101MHz, CDCl3, 298K, δ): 205.9, 191.9, 163.9, 132.1, 128.0, 113.6, 83.0, 58.4, 55.4, 26.8, 23.8, 19.6, 13.6.

[0377] Experimental Example 107: Preparation of 1-(4-ethylformylbenzene)-1,3-butanedione-α-sulfuric acid

[0378]

[0379] The experimental procedure is described in Example 104, 1-(4-ethylformylbenzene)-1,3-butanedione-α-tetrabutylammonium sulfate (90%). 1 H-NMR yield). 1 H NMR (400MHz, CDCl3, 298K, δ): 15.19*(s,0.4H),8.22*(d,J=8.2Hz,0.8H),8.16(d,J=8.0Hz,2H),8.06(d,J=8.1Hz,2H),7.99*(d,J=8.1Hz,0.8 H),5.82(s,1H),4.39-4.31(m,3H),3.16–3.13(m,11H),2.50*(s,1H), 2.37(s,3H),1.56(s,11H),1.39-1.32(m,15H),0.94(t,J=6.7Hz,17H); 13 C NMR (101MHz, CDCl3, 298K, δ): 205.2,197.4*,193.6,171.9*,166.2*,165.7,138.8*,138.1,134.3,131.6* ,130.5*,129.49,129.45,129.2*,128.7*,83.3,61.3,60.9*,58.5,26.9,24.0*,23.8,19.6,14.2*,13.5.

[0380] Experimental Example 108: Preparation of 1-(2-chlorobenzene)-1,3-butanedione-α-sulfuric acid

[0381]

[0382] The experimental procedure is described in Example 104, 1-(2-chlorobenzene)-1,3-butanedione-α-tetrabutylammonium sulfate (47%). 1 H-NMR yield). 1 H NMR (400MHz, CDCl3, 298K, δ): 14.75*(s,0.8H),7.81(d,J=7.4Hz,1H),7.62*(d,J=6.7Hz,0.8H),7.39-7.36(m,2H),7.34–7.31(m, 2H),7.25-7.21(m,1H),5.82(s,1H),3.18(s,14H),2.46*(s,2H),2.35(s,3H),1.58(s,14H),1.37(s,14H),0.96(t,J=5.7Hz,22H); 13 C NMR (101MHz, CDCl3, 298K, δ): 203.5, 195.1, 193.4*, 178.2*, 135.9*, 134.7*, 132.2, 132.1*, 132. 0*,131.2*,130.9,130.6,130.2,129.3,126.6,125.9*,85.5,58.6,27.1,23.9,23.1*,19.7,13.6.

[0383] Experimental Example 109: Preparation of 1-(3-chlorobenzene)-1,3-butanedione-α-sulfuric acid

[0384]

[0385] The experimental procedure is described in Example 104, 1-(3-chlorobenzene)-1,3-butanedione-α-tetrabutylammonium sulfate (93%). 1 H-NMR yield). 1H NMR (400MHz, CDCl3, 298K, δ): 15.22* (s, 0.3H), 8.14* (dt, J = 7.3, 1.6Hz, 0.3H), 8.0 8*(t,J=1.9Hz,0.3H),8.05–8.01(m,2H),7.50-7.47(m,1H),7.36(t,J=7.9Hz,1H),7 .33–7.30*(m,0.3H),7.28*(s,0.3H),5.76(s,1H),3.17–3.13(m,10H),2.47*(s,0.8 H),2.36(s,3H),1.61–1.53(m,10H),1.35(h,J=7.3Hz,10H),0.94(t,J=7.3Hz,16H); 13 C NMR (101MHz, CDCl3, 298K, δ): 205.1,196.3*,192.7,172.4*,136.5,134.5,133.4*,133.3,130. 4*,130.3*,129.8,129.2,128.99*,128.96*,128.1,128.0*,83.3,58.4,26.8,23.7,19.5,13.5.

[0386] Experimental Example 110: Preparation of 1-(3-methoxybenzene)-1,3-butanedione-α-sulfuric acid

[0387]

[0388] The experimental procedure is described in Example 104, 1-(3-methoxybenzene)-1,3-butanedione-α-tetrabutylammonium sulfate (89%). 1 H-NMR yield). 1 H NMR (400MHz, CDCl3, 298K, δ): 15.43* (s, 0.1H), 7.85* (t, J=2.1Hz, 0.1H), 7.79* (d, J=7.9, 0.1H) ,7.72(d,J=7.7,1H),7.65(t,J=2.1Hz,1H),7.31(t,J=8.0Hz,1H),7.22*(d,J=8.0Hz,0.1H),7.07 (dd,J=8.2,2.5,1H),6.91*(dd,J=8.2,2.5,1H,0.1H),5.80(s,1H),3.81(s,3H),3.17–3.13(m,9H ),2.48*(s,0.3H),2.35(s,3H),1.59-1.51(m,9H),1.34(h,J=7.3Hz,9H),0.93(t,J=7.3Hz,13H);13 C NMR (101MHz, CDCl3, 298K, δ):205.6,195.9*,193.4,173.8*,159.6,158.9*,136.1,135.8*,129.4 ,128.5*,122.3,122.0*,120.5,117.7*,114.0*,113.5,83.0,58.3,55.5,26.8,23.7,19.5,13.5.

[0389] Experimental Example 111: Preparation of 1-phenyl-4,4-dimethyl-1,3-pentanedione-α-sulfuric acid

[0390]

[0391] The experimental procedure is described in Example 104, using 1-phenyl-4,4-dimethyl-1,3-pentanedione-α-tetrabutylammonium sulfate (58%). 1 H-NMR yield). 1 H NMR (400MHz, CDCl3, 298K, δ): 8.22 (d, J = 7.8Hz, 2H), 7.52 (t, J = 7.4Hz, 1H), 7.43 (t, J = 7.6Hz, 2H), 6.44 ( s,1H),3.26–3.21(m,8H),1.65–1.57(m,8H),1.36(h,J=7.4Hz,8H),1.21(s,9H),0.94(t,J=7.3Hz,12H); 13 CNMR (101MHz, CDCl3, 298K, δ): 209.0, 194.9, 135.4, 133.2, 129.8, 128.4, 58.6, 44.4, 26.5, 23.9, 19.6, 13.6. Example 112: Preparation of 1-phenyl-3-(2-thiophene)-1,3-propanedione-α-sulfuric acid.

[0392]

[0393] The experimental procedure is described in Example 104, using 1-phenyl-3-(2-thiophene)-1,3-butanedione-α-tetrabutylammonium sulfate (62%). 1 H-NMR yield). 1H NMR (400MHz, CDCl3, 298K, δ): 8.29 (d, J = 3.8Hz, 1H), 8.12 (d, J = 7.3Hz, 2H), 7.62 (d, J = 4.9Hz, 1H), 7.51 (t, J = 7.4Hz, 1H), 7.40 (t, J = 7.6Hz,2H),7.09(t,J=4.4Hz,1H),6.48(s,1H),3.19–3.14(m,8H),1.60-1.52(m,8H),1.33(q,J=7.3Hz,8H),0.92(t,J=7.3Hz,12H); 13 C NMR (101MHz, CDCl3, 298K, δ): 193.9, 187.4, 141.5, 135.7, 135.2, 134.4, 133.2, 129.6, 128.5, 128.3, 82.1, 58.4, 23.8, 19.6, 13.6.

[0394] Experimental Example 113: Preparation of 1-phenyl-3-(4-bromobenzene)-1,3-propanedione-α-sulfuric acid

[0395]

[0396] The experimental procedure is described in Example 104, using 1-phenyl-3-(4-bromobenzene)-1,3-butanedione-α-tetrabutylammonium sulfate (80%). 1 H-NMR yield). 1 H NMR (400MHz, CDCl3, 298K, δ): 8.09 (d, J = 7.8Hz, 2H), 7.99 (d, J = 8.2Hz, 2H), 7.85* (d, J = 8.2Hz, 0.2H), 7.51 (d, J = 8.5H z,3H),7.39(t,J=7.6Hz,2H),6.62(s,1H),3.18-3.15(m,9H),1.57(s,9H),1.38-1.31(m,9H),0.93(t,J=6.9Hz,13H); 13 C NMR(101MHz,CDCl3,298K,δ):194.3,194.0,135.2,134.1,133.4,132.2*,131.7,1 31.5*,131.3,130.8,129.6,129.3*,128.9*,128.5,81.6,58.6,23.9,19.7,13.7.

[0397] Experimental Example 114: Preparation of 1,3-(4-methoxybenzene)-1,3-propanedione-α-sulfuric acid

[0398]

[0399] The experimental procedure is described in Example 104, using di-1,3-(4-methoxybenzene)-1,3-butanedione-α-tetrabutylammonium sulfate (50%). 1 H-NMR yield). 1 H NMR (400MHz, CDCl3, 298K, δ): 8.13 (d, J = 8.6Hz, 4H), 6.87 (d, J = 8.7Hz, 4H), 6.64 (s, 1H), 3.82 (s,6H),3.23–3.19(m,8H),1.63-1.53(m,8H),1.36(h,J=7.3Hz,8H),0.93(t,J=7.3Hz,12H); 13 C NMR (101MHz, CDCl3, 298K, δ): 192.8, 163.6, 132.0, 128.4, 113.6, 81.3, 58.5, 55.4, 23.9, 19.6, 13.6.

[0400] Experimental Example 115: Preparation of 1-thiophene-1,3-butanedione-α-sulfuric acid

[0401]

[0402] The experimental procedure is described in Example 104, 1-thiophene-1,3-butanedione-α-tetrabutylammonium sulfate (72%). 1 H-NMR yield). 1 H NMR (400MHz, CDCl3, 298K, δ): 15.35* (s, 0.1H), 8.33* (dd, J=3.9, 1.1Hz, 0.1H), 8.20 (dd ,J=3.9,1.1Hz,1H),7.64(dd,J=5.0,1.1Hz,1H),7.52*(dd,J=5.0,1.2Hz,0.1H),7.09(d d,J=4.9,3.9Hz,1H),7.06*(dd,J=5.0,3.9Hz,0.1H),5.64(s,1H),3.20–3.15(m,9H),2. 40*(s,0.3H),2.34(s,3H),1.61-1.53(m,9H),1.40–1.31(m,9H),0.93(t,J=7.3Hz,13H); 13 C NMR (101MHz, CDCl3, 298K, δ): 204.6, 186.2, 141.4, 135.8, 134.8, 128.5, 84.1, 58.4, 26.7, 23.7, 19.5, 13.5.

[0403] Experimental Example 116: Preparation of 1-Methyl-5-acetylpyrrole-2-sulfuric acid

[0404]

[0405] 1-Methyl-2-acetylpyrrole (0.2 mmol), silver carbonate (0.02 mmol), ligand (0.02 mmol), ammonium persulfate (0.6 mmol), tetrabutylammonium persulfate (0.1 mmol), and lithium carbonate (0.2 mmol) were added sequentially to a 4 mL reaction flask. After the additions, the 4 mL reaction flask was sealed and evacuated, then purged with argon gas. This process was repeated three times. Finally, 1.0 mL of dichloromethane was added to the flask, and the mixture was allowed to react at room temperature for 10 hours. After the reaction was complete, 200 mg of sodium bicarbonate was added to quench the reaction, and the organic phase was collected by filtration. The organic phase was concentrated and subjected to column chromatography. 1-Methyl-5-acetylpyrrole-2-tetrabutylammonium sulfate (56%) was separated using a dichloromethane to methanol eluent at a volume ratio of 20:1. 1 H-NMR yield). 1 H NMR (400MHz, CDCl3, 298K, δ): 7.41 (d, J=6.0Hz, 1H), 6.20 (d, J=6.0Hz, 1H), 3.27–3.17 (m, 10H), 2.89 (s, 3H), 2.39 (s, 3H), 1.72–1.55 (m, 10H), 1.43 (m, 10H), 1.01 (t, J = 7.3Hz, 14H).

[0406] Experimental Example 117: Preparation of 5-methylacetate furan-2-sulfuric acid

[0407]

[0408] The experimental procedure is described in Example 116, 5-methylacetate furan-2-sulfate tetrabutylammonium (45%). 1 H-NMR yield). 1 H NMR (400MHz, CDCl3, 298K, δ): 7.64 (d, J = 5.7Hz, 1H), 6.13 (d, J = 5.7Hz, 1H), 4.47 (d, J = 11.5Hz, 1H), 4.26 (d,J=11.5Hz,1H),3.24–3.14(m,10H),1.98(s,3H),1.60(m,10H),1.40(m,10H),0.97(t,J=7.3Hz,15H); 13C NMR (101MHz, CDCl3, 298K, δ): 170.2, 170.0, 152.3, 123.4, 105.4, 64.1, 58.5, 23.8, 20.6, 19.6, 13.6.

[0409] Experimental Example 118: Preparation of Sodium 1-Phenylacetane-1,3-Disulfate

[0410]

[0411] Add 0.2 mmol of phenylcyclopropane, 0.02 mmol of silver nitrate, 0.02 mmol of ligand, 0.6 mmol of ammonium persulfate, and 0.6 mmol of tetrabutylammonium hydrogen sulfate sequentially to a 4 mL reaction flask. After the additions, seal the 4 mL reaction flask, evacuate it, and then purge it with argon gas. Repeat this process three times. Finally, add 1.0 mL of dichloromethane to the flask and allow it to react at room temperature for 10 hours. After the reaction is complete, quench the reaction with 200 mg of sodium bicarbonate, and then filter to collect the organic phase. Concentrate the organic phase and perform column chromatography. Separate 1-phenylpropane-1,3-disulfate tetrabutylammonium using a dichloromethane to methanol eluent ratio of 20:1. Finally, perform ion exchange to obtain sodium 1-phenylpropane-1,3-disulfate (88%). 1 H-NMR yield). 1 H NMR(400MHz,D2O,298K,δ):7.44–7.33(m,5H),5.40(t,J=6.8,1H),4.12(m,1 H),3.96(m,1H),2.34(dt,J=13.9,7.0Hz,1H),2.17(dt,J=14.3,6.5Hz,1H); 13 C NMR (101MHz, D2O, 298K, δ): 139.6, 128.7, 128.5, 126.6, 78.7, 65.4, 36.4.

[0412] Experimental Example 119: Preparation of 1-(4-bromophenyl)propane-1,3-disulfuric acid

[0413]

[0414] The experimental procedure is described in Example 118, using 1-(4-bromophenyl)propane-1,3-disulfate tetrabutylammonium (99%). 1 H-NMR yield). 1H NMR (400MHz, CD3OD, 298K, δ): 7.47(d,J=8.5Hz,2H),7.38–7.32(m,2H),5.41(t,J=6.7Hz,1H),4.08(m,1H),3.96(m,1H),3.27–3.18(m,16H) ,2.35(dt,J=14.4,7.2Hz,1H),2.16(dt,J=13.7,6.7Hz,1H),1.66(dd,J=10.6,6.0Hz,16H),1.41(q,J=7.4Hz,17H),1.02(t,J=7.4Hz,24H); 13 C NMR (101MHz, CD3OD, 298K, δ): 140.5, 130.9, 128.3, 120.9, 76.5, 64.1, 58.1, 37.0, 23.4, 19.2, 12.6.

[0415] Experimental Example 120: Preparation of 1-(4-chlorobenzene)propane-1,3-disulfuric acid

[0416]

[0417] The experimental procedure is described in Example 118, 1-(4-chlorobenzene)propane-1,3-disulfate tetrabutylammonium (74%). 1 H-NMR yield). 1 H NMR (400MHz, CD3OD, 298K, δ): 7.41 (d, J = 8.4Hz, 2H), 7.32 (d, J = 8.4Hz, 2H), 5.4 3(t,J=6.8Hz,1H),4.09(dt,J=10.2,6.5Hz,1H),3.96(dt,J=10.2,7.1Hz,1H), 3.27–3.20(m,16H),2.35(dd,J=14.0,7.1Hz,1H),2.14(dd,J=13.6,6.8Hz,1H) ,1.66(dd,J=10.4,6.2Hz,17H),1.41(q,J=7.4Hz,17H),1.02(t,J=7.3Hz,25H); 13 C NMR (101MHz, CD3OD, 298K, δ): 141.4, 134.2, 129.3, 129.3, 77.8, 65.5, 59.5, 38.5, 24.8, 20.7, 14.0. Experimental Example 121: Preparation of 1-(4-tert-butylbenzene)propane-1,3-disulfuric acid.

[0418]

[0419] The experimental procedure is described in Example 118, 1-(4-tert-butylbenzene)propane-1,3-disulfate tetrabutylammonium (72%). 1 H-NMR yield). 1 H NMR (400MHz, CD3OD, 298K, δ): 7.39–7.32(m,4H),5.42(t,J=6.8Hz,1H),4.07(td,J=9.1,8.7,5.6Hz,1H),3.97(dt,J=10.1,7.4Hz,1H),3.28–3.15(m ,16H),2.40(dq,J=14.4,7.2Hz,1H),2.18(dq,J=13.6,6.7Hz,1H),1.72–1 .60(m,16H),1.42(q,J=7.4Hz,17H),1.30(s,9H),1.02(t,J=7.3Hz,24H); 13 C NMR (101MHz, CD3OD, 298K, δ): 151.6, 139.3, 127.4, 126.1, 78.6, 65.8, 59.5, 38.5, 35.3, 31.8, 24.8, 20.7, 14.0.

[0420] Experimental Example 122: Preparation of 1-(4-isopropylphenyl)propane-1,3-disulfuric acid

[0421]

[0422] The experimental procedure is described in Example 118, 1-(4-isopropylphenyl)propane-1,3-disulfate tetrabutylammonium (78%). 1 H-NMR yield). 1 H NMR (400MHz, CD3OD, 298K, δ): 7.33 (d, J=7.9Hz, 2H), 7.19 (d, J=8.0Hz, 2H), 5.41 (t, J= 6.8Hz,1H),4.07(td,J=9.1,8.4,5.6Hz,1H),3.97(dt,J=10.0,7.3Hz,1H),3.27–3.20( m,16H),2.88(p,J=6.9Hz,1H),2.39(dt,J=14.4,7.1Hz,1H),2.22–2.13(m,1H),1.66(t ,J=8.3Hz,16H),1.42(q,J=7.4Hz,16H),1.23(d,J=6.9Hz,6H),1.02(t,J=7.3Hz,24H); 13C NMR (101MHz, CD3OD, 298K, δ): 149.4, 139.7, 127.7, 127.2, 78.6, 65.8, 59.5, 38.5, 35.1, 24.8, 24.5, 20.7, 14.0.

[0423] Experimental Example 123: Preparation of 1-(4-acetoxyphenyl)propane-1,3-disulfuric acid

[0424]

[0425] The experimental procedure is described in Example 118, using 1-(4-acetoxyphenyl)propane-1,3-disulfate tetrabutylammonium (93%). 1 H-NMR yield). 1 H NMR (400MHz, CD3OD, 298K, δ): 7.48 (d, J = 8.3Hz, 2H), 7.08 (d, J = 8.3Hz, 2H), 5.47 (t,J=6.8Hz,1H),4.12(td,J=9.1,8.3,5.7Hz,1H),4.01(dt,J=10.3,7.3Hz,1H), 3.29–3.20(m,16H),2.40(dt,J=14.4,7.2Hz,1H),2.28(s,3H),2.21(dt,J=13.6 ,6.8Hz,1H),1.66(d,J=8.0Hz,16H),1.43(q,J=7.4Hz,16H),1.07–1.01(m,24H); 13 CNMR(101MHz,CD3OD,298K,δ):171.0,151.7,140.1,128.7,122.4,78.0,65.7,59.5,38.6,24.8,20.9,20.7,14.0.

[0426] Experimental Example 124: Preparation of Sodium 1-(4-methylformylbenzene)propane-1,3-disulfate

[0427]

[0428] The experimental procedure is described in Example 118, using sodium 1-(4-methylcarboxyphenyl)propane-1,3-disulfate (49%). 1 H-NMR yield). 1H NMR (400MHz, D2O, 298K, δ): 8.02 (dd, J=8.3, 2.0Hz, 2H), 7.55 (d, J=8.1Hz, 2H), 5.48 (t, J=6.8Hz, 1H), 4.16 (dt, J=12.4,6.1Hz,1H),4.01(dt,J=11.2,6.1Hz,1H),3.91(s,3H),2.41–2.30(m,1H),2.20(dd,J=14.2,6.7Hz,1H); 13 C NMR (101MHz, D2O, 298K, δ): 169.2, 145.4, 129.7, 129.4, 126.7, 77.9, 65.1, 52.7, 36.2.

[0429] Many specific details have been set forth in the foregoing description to provide a full understanding of the present invention. However, the above description is merely a preferred embodiment of the present invention, and the present invention can be implemented in many other ways different from those described herein. Therefore, the present invention is not limited to the specific embodiments disclosed above. Furthermore, any person skilled in the art can make many possible variations and modifications to the technical solutions of the present invention, or modify them into equivalent experimental examples, using the methods and techniques disclosed above, without departing from the scope of the present invention. Any simple modifications, equivalent changes, and modifications made to the above experimental examples based on the technical essence of the present invention, without departing from the content of the present invention, shall still fall within the scope of protection of the present invention.

Claims

1. A method for producing an organic sulfate salt, characterized in that, the organic sulfate salt is sodium 2-phenyl-1-ethyl sulfate, and the production process is: Into a 4 mL reaction vial, 2-phenyl-1-ethylboronic acid pinacol ester 0.2 mmol, ammonium persulfate 0.4 mmol, tetrabutylammonium hydrogen sulfate 0.24 mmol, sodium fluoride 0.2 mmol were added sequentially; after addition, the 4 mL reaction vial was sealed, vacuumed, and backfilled with argon, which was repeated three times; finally, 1 mL of tetrahydrofuran was added to the vial and the reaction was allowed to proceed at room temperature for 12 hours; after the reaction was complete, sodium bicarbonate was added to quench the reaction, and the organic phase was collected; the organic phase was concentrated and column chromatography was performed using dichloromethane and methanol in a 20:1 volume ratio as the eluent to isolate 2-phenyl-1-ethyl tetrabutylammonium sulfate, which was then subjected to ion exchange to obtain sodium 2-phenyl-1-ethyl sulfate, and 1 H-NMR yield 86%.

2. A method for producing an organic sulfate salt, characterized in that, the organic sulfate salt is sodium 3-phenylpropyl sulfate, and the production process is: Into a 4 mL reaction vial, 3-phenyl-1-propanol 0.2 mmol, potassium persulfate 0.4 mmol, tetrabutylammonium hydrogen sulfate 0.24 mmol were added sequentially; after the addition, the 4 mL reaction vial was sealed, vacuumed, and then filled with argon, which was repeated 3 times; finally, 1 mL of N,N-dimethylformamide was added to the vial and placed in an 80 °C oven for 12 hours; after the reaction was completed, water and dichloromethane were added to quench the reaction, and then the organic phase was collected; the organic phase was concentrated and then column chromatography was performed using dichloromethane and methanol in a volume ratio of 20:1 as the eluent to separate 3-phenylpropyl tetrabutylammonium sulfate, which was then subjected to ion exchange to obtain sodium 3-phenylpropyl sulfate. 1 H-NMR yield 97%.

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